The association between tobacco and the risk of asthma, rhinoconjunctivitis and eczema in children and adolescents: analyses from Phase Three of the ISAAC programme.
Exposure to parental smoking is associated with wheeze in early childhood, but in 2006 the US Surgeon General stated that the evidence is insufficient to infer a causal relationship between exposure and asthma in childhood and adolescents. To examine the association between maternal and paternal smoking and symptoms of asthma, eczema and rhinoconjunctivitis. Parents or guardians of children aged 6-7 years completed written questionnaires about symptoms of asthma, rhinoconjunctivitis and eczema, and several risk factors, including maternal smoking in the child's first year of life, current maternal smoking (and amount) and paternal smoking. Adolescents aged 13-14 years self completed the questionnaires on these symptoms and whether their parents currently smoked. In the 6-7-year age group there were 220 407 children from 75 centres in 32 countries. In the 13-14-year age group there were 350 654 adolescents from 118 centres in 53 countries. Maternal and paternal smoking was associated with an increased risk of symptoms of asthma, eczema and rhinoconjunctivitis in both age groups, although the magnitude of the OR is higher for symptoms of asthma than the other outcomes. Maternal smoking is associated with higher ORs than paternal smoking. For asthma symptoms there is a clear dose relationship (1-9 cigarettes/day, OR 1.27; 10-19 cigarettes/day, OR 1.35; and 20+ cigarettes/day, OR 1.56). When maternal smoking in the child's first year of life and current maternal smoking are considered, the main effect is due to maternal smoking in the child's first year of life. There was no interaction between maternal and paternal smoking. This study has confirmed the importance of maternal smoking, and the separate and additional effect of paternal smoking. The presence of a dose-response effect relationship with asthma symptoms suggests that the relationship is causal, however for eczema and rhinoconjunctivitis causality is less certain.


Similarities and differences between frozen-hydrated, rigor acto-S1 complexes of insect flight and chicken skeletal muscles.
The structure and function of myosin crossbridges in asynchronous insect flight muscle (IFM) have been elucidated in situ using multiple approaches. These include generating "atomic" models of myosin in multiple contractile states by rebuilding the crystal structure of chicken subfragment 1 (S1) to fit IFM crossbridges in lower-resolution electron microscopy tomograms and by "mapping" the functional effects of genetically substituted, isoform-specific domains, including the converter domain, in chimeric IFM myosin to sequences in the crystal structure of chicken S1. We prepared helical reconstructions (approximately 25 A resolution) to compare the structural characteristics of nucleotide-free myosin0 S1 bound to actin (acto-S1) isolated from chicken skeletal muscle (CSk) and the flight muscles of Lethocerus (Leth) wild-type Drosophila (wt Dros) and a Drosophila chimera (IFI-EC) wherein the converter domain of the indirect flight muscle myosin isoform has been replaced by the embryonic skeletal myosin converter domain. Superimposition of the maps of the frozen-hydrated acto-S1 complexes shows that differences between CSk and IFM S1 are limited to the azimuthal curvature of the lever arm: the regulatory light-chain (RLC) region of chicken skeletal S1 bends clockwise (as seen from the pointed end of actin) while those of IFM S1 project in a straight radial direction. All the IFM S1s are essentially identical other than some variation in the azimuthal spread of density in the RLC region. This spread is most pronounced in the IFI-EC S1, consistent with proposals that the embryonic converter domain increases the compliance of the IFM lever arm affecting the function of the myosin motor. These are the first unconstrained models of IFM S1 bound to actin and the first direct comparison of the vertebrate and invertebrate skeletal myosin II classes, the latter for which, data on the structure of discrete acto-S1 complexes, are not readily available.


[Antibody Screening and Risk Assessment of Healthcare Professionals in the COVID-19 Pandemic].
Globally 364102 healthcare professionals have been infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and 1253 of them died until 15 January 2021. Healthcare professionals serving at the forefront of combating the pandemic are in the high risk group. In our country, the data about coronavirus-2019 (COVID-19) among healthcare professionals are limited. The aim of this study was to investigate the anti-SARS-CoV-2 IgG seroprevalence in healthcare professionals, to evaluate the risks they encountered during work, and to examine their relationships with antibody positivity. A total of 572 healthcare professionals serving in various units of our hospital participated in our study and the presence of anti-nucleocapsid IgG was investigated by chemiluminescent microparticle immunoassay (SARS-CoV-2 IgG test, Abbott Laboratories Diagnostics, USA) method in serum samples collected between May 18, 2020 and June 30, 2020. The demographic characteristics, medical history, work conditions, medical procedures performed and possible risk factors were questioned with a questionnaire form. The average age of the participants was 33.5 ± 9.2 (19-61) years, and 62.9% (360/572) of them were women. In our study, the anti-SARS-CoV-2 IgG seroprevalence was 3.7% (21/572). The association of the antibody positivity with age, gender and occupational status was not statistically significant (p> 0.05). Comorbid diseases which were significantly higher in seropositive healthcare professionals were hypertension (19%) and diabetes mellitus (14.3%) (p<0.05). It was observed that antibody positivity was significantly higher in healthcare professionals working in high (52.4%) and medium risk (33.3%) areas, those who treat and/or examine patients with suspicious or positive COVID-19 (66.7%) and those who spend more than 30 minutes in COVID-19 patient rooms (76%) (p<0.05). The symptoms associated with seropositivity in healthcare workers with a history of symptoms (46%) were loss of smell (23.5%), loss of taste (20.0%) and respiratory distress (16.7%) (p<0.05). It was observed that the probability of being infected with SARS-CoV-2 increased 12 times if there was a colleague with COVID-19 in the hospital, four times if there was a patient in the house/lodging and six times if there was an infected person in the social environment (p<0.05). The rate of those who had the flu vaccine among the participants was 10.8% (62/572) and 9.7% of them were found to be anti-SARS-CoV-2 IgG positive (p<0.05, 95% CI= 1.31-9.48). The seropositivity was significantly higher in non-smokers (4.8 %) compared to smokers (0.0%) (p<0.05). In our study, it was determined that the rate of seropositivity was 12 times higher in healthcare professionals who stated that they received hydroxychloroquine prophylaxis due to risky contact compared to those who did not receive prophylaxis (p<0.05, 95% CI= 4.11-40.64). The ratio of the personnel who answered "always" to the frequency of wearing gloves, masks, goggles/face shields and overalls was 85.7%, 96.9%, 62.1% and 65.4%, respectively. In conclusion, regular and large-scale seroepidemiological screening of healthcare professionals in the COVID-19 pandemic can contribute to the control of the pandemic by providing a better understanding of transmission dynamics and risk factors.


Comparative evaluation of the API 20S system and the automicrobic system gram-positive identification card for species identification of streptococci.
Two commercial methods, the API 20S system (API; Analytab Products, Inc., Plainview, N.Y.) and the Gram-Positive Identification Card (GPI; Vitek Systems, Inc., Hazelwood, Mo.), were evaluated without additional tests for the identification of 241 streptococcus strains. Organisms included 60 beta-hemolytic strains, 36 group D strains, 26 Streptococcus pneumoniae strains, and 119 viridans streptococcus strains. API correctly identified to species 68.3% of beta-hemolytic strains, 86.1% of group D strains, 53.9% of S. pneumoniae strains, and 12.6% of viridans streptococci. This method provided excellent identification of group A and B and S. faecalis strains. Overall, API correctly identified 41.9% of strains to species, with 41.1% good likelihood but low selectivity, 15.8% incorrect, and 1.2% not identified. GPI correctly identified to species 58.3% of beta-hemolytic strains, 97.2% of group D strains, 80.8% of S. pneumoniae strains, and 57.2% of viridans streptococci. Group A, B, and D strains were all accurately identified by this system. Overall, GPI correctly identified to species 66.0% of strains, with 8.7% correct preliminary identification, 20.8% incorrect, and 4.6% not identified. Both methods represent a worthwhile advance in streptococcal identification. Neither system, however, can be recommended for species identification of the viridans group at this time.


Granule-based immobilization and activity enhancement of anammox biomass via PVA/CS and PVA/CS/Fe gel beads.
Granule-based immobilization of anammox biomass assisted by polyvinyl alcohol/chitosan (PVA/CS) and PVA/CS/Fe gel beads was studied, via the operation of three identical up-flow reactors (R1 without gel beads, R2 with PVA/CS, R3 with PVA/CS/Fe) for 203 days. In the end, the nitrogen removal rates (NRR) were 5.3 ± 0.4, 10.0 ± 0.3 and 13.9 ± 0.5 kg-N m-3 d-1 for R1, R2 and R3, respectively. The porous PVA/CS and PVA/CS/Fe created a suitable eco-niche for anammox bacteria to grow and attach, thus being retained in the reactor. The EPS entangles newly grown cells within the gel beads, resulting in compact aggregation. The interaction between Fe ions added to PVA/CS/Fe gel beads and negatively charged EPS groups strongly promoted granule strength and compactness. The immobilization method proposed by this study was found to effectively improve biomass retention in the reactors, which is promising for advanced anammox process applications.


Analysis of the Reform Effectiveness of Vocational Skill Identification Based on the New Social Training Model in the New Era under Deep Learning Assessment.
In order to be able to make full use of domain knowledge to improve the performance of skill word extraction, this paper proposes a skill word extraction method based on a combination of deep learning and corpus features. Skill word extraction is transformed into a sequence annotation problem, and based on the basic model of sequence annotation, Bi-LSTM-CRF, corpus features are added to the input layer, and the output of the input layer is connected with the Bi-LSTM output as the input of the CRF layer. The experimental results show timely updating of the question bank, paying attention to the quality of vocational skill identification, and strictly managing the issuance of vocational qualification false certificates.


Testing a model of absence and intent to stay in employment: a study of registered nurses in Malta.
This study used a cross-sectional, correlational design to test a model of absence and turnover of registered nurses developed from a review of the research literature (Gauci Borda and Norman, 1997). Testing the model involved comparing the relationship between job satisfaction, kinship responsibility, pay, employment opportunity, intent to stay in employment and absence for male and female registered nurses. All registered nurses (n = 254) working in clinical areas on a full-time shift basis, in one large general hospital in Malta were surveyed by questionnaire and their absence data were obtained from the hospital personnel records. A response rate of 67% (n = 171) was achieved. The results showed that nurses were satisfied with their job and intended to stay in their present employment for the next 12 months. Relationships between variables differed between male and female nurses, with job satisfaction being associated with intent to stay for male nurses but not for females and kinship responsibility and intent to stay being associated with absence in female but not male nurses. In contrast to many previous studies of nurses, an association was found between job satisfaction and absence. Several variables, including fear of change, which may influence intent to stay of Maltese nurses, were identified. The proposed model of absence and turnover stood up reasonably well to testing, but the results for the whole sample, and the sub-samples of male and female nurses supported different parts of the model. The main implication for future research is that male and female nurses should be studied separately due to differences found between the two groups.


Over-expression of K-FGF or bFGF results in altered expression of matrix metalloproteinases: correlations with malignant progression and cellular invasion.
Matrix metalloproteinase (MMP) expression was investigated in NIH-3T3 fibroblasts that secrete K-FGF and in NIH-3T3 cells which express chimeric bFGF with a signal sequence targeting bFGF to the secretory pathway. Correlations between altered MMPs' and other proteases' expression and malignant potential were determined. Correlations between the expression of MMPs and the invasion ability of K-FGF and bFGF over-expressing cells were also determined. The resulting correlation between alterations in proteases and malignant progression supports a model which suggests that growth factor modulation of protease expression is part of the altered growth regulatory program associated with cellular transformation and malignant progression.


Unexpected cross-species contamination in genome sequencing projects.
The raw data from a genome sequencing project sometimes contains DNA from contaminating organisms, which may be introduced during sample collection or sequence preparation. In some instances, these contaminants remain in the sequence even after assembly and deposition of the genome into public databases. As a result, searches of these databases may yield erroneous and confusing results. We used efficient microbiome analysis software to scan the draft assembly of domestic cow, Bos taurus, and identify 173 small contigs that appeared to derive from microbial contaminants. In the course of verifying these findings, we discovered that one genome, Neisseria gonorrhoeae TCDC-NG08107, although putatively a complete genome, contained multiple sequences that actually derived from the cow and sheep genomes. Our findings illustrate the need to carefully validate findings of anomalous DNA that rely on comparisons to either draft or finished genomes.


Non-random association between DNA markers and Huntington disease locus in the Italian population.
A group of Huntington disease (HD) families of Italian ancestry was analyzed for 11 RFLPs from genetic loci mapped in 4p16 and genetically linked to the HD gene. We found a statistically significant difference of allele distributions in HD vs normal chromosomes for loci D4S10, D4S127, and D4S43. This observation increases the number of loci in linkage disequilibrium with HD. However, the amount of disequilibrium does not allow either a finer localization of the HD gene or a substantial improvement in risk calculations.


Association of colonic diverticular disease and irritable bowel syndrome in Thai patients.
Colonic diverticular disease exhibits mucosal outpouchings through the large intestine. Common complications of this disease are diverticular bleeding and diverticulitis. Some patients with colonic diverticular disease have abdominal symptoms resembling irritable bowel syndrome (IBS). IBS is a functional gastrointestinal disorder with abdominal discomfort, bloating or pain associated with disturbed defecation and unclear etiology. Some studies have shown a high prevalence of colonic diverticular disease in patients with IBS. To determine the association, clinical characteristics and factors associated with colonic diverticular disease in IBS patients compared with a control group. A cross-sectional prospective study was conducted at the Gastroenterology Unit, Department of Medicine, Rajavithi Hospital, Bangkok during December 2007 to January 2009. The study collected data regarding clinical characteristics, demographics and colonoscopic findings of colonic diverticular disease comparing among IBS patients, defined by Rome III criteria and control group patients. The study was approved by the institutional ethics committee of Rajavithi Hospital. Demographic data of patients were collected. The presence of diverticula, their location and number from colonoscopic findings were recorded. One hundred and fifty patients were enrolled and analyzed. The patients comprised 75 patients in the IBS group and 75 patients in the control group. The prevalence ofcolonic diverticular disease in the total population was 17.3% (26 of 150). The IBS group had a higher prevalence of colonic diverticular disease than the control group with statistical significance (18 of 75, 24.0% in the IBS group vs. 8 of 75 or 10.7% in the control group, p = 0.031). Body mass index (BMI) more than 25 kg/m2, age more than 60 years and being male were associated with colonic diverticular disease without significance (28.1% in BMI >25 kg/m2 vs. 14.3% in BMI ≤25 kg/m2, p = 0.071, 23.0% in age >60 years vs. 13.5% in age ≤60 years, p = 0.132 and 20.3% males vs. 15.1% females, p = 0.406). Type of IBS (IBS-C vs. IBS-D) did not affect the prevalence of colonic diverticular disease (25.8% in IBS-C and 23.1% in IBS-D, p = 0.791). There were no difference in the location of colonic diverticular disease and number ofdiverticuli between the IBS group and control group (p = 0.149 and 0.095). An increased frequency of colonic diverticular disease was observed in patients with IBS. Increasing age, high BMI and being male were factors associated with colonic diverticular disease. These results suggest that IBS and colonic diverticular disease may have a common pathogenesis.


[Knee instability and varus malangulation - Simultaneous cruciate ligament reconstruction and osteotomy (Indication, planning and operative technique, results)].
Osteochondral lesions and osteoarthritis in young patients are often caused by chronic knee instability in varus malangulated knees. We present the indication, planning of the osteotomy as well as the operative technique and the results of our patients with simultaneous osteotomy and cruciate ligament reconstruction. From 4/96 until 12/00 58 patients ( 33 years) received simultaneous osteotomy (r = 57 correcting valgus, r = 1 varus malalignement) and cruciate ligament plasty (e = 49 ACL, n = 7 PCL, n = 2 ACL & PCL which routinely was performed in the arthroscopic technique after completion of the osteotomy (closed-wedge technique). Average correction angle of the osteotomy was 7 (4 - 10) degrees with a mean malalignement of 5 (0 - 10) degrees. 13 patients underwent additional cartilage surgery (osteochondral autograft transplantation, autologous chondrocyte transplantation, microfracturing), 2 patients received an implanted Collagen Meniscus (CMI) at the same time. Preoperatively the Lysholm score was 66 (35 - 81) points and increased to 81 (74 - 95), 87 (79 - 99) and 93 (88 - 99) points at 3, 6, and 12 months after surgery, respectively. Subjectively all patients reported an improvement of preoperative swelling, pain and instability. Additional cartilage surgery or meniscus implantation did not significantly alter the clinical score values. Complications were noted in 4 patients. Unstable varus malangulated knees can be sufficiently treated by osteotomy and cruciate ligament plasty at the same time, suggesting that unicompartimental decompression and treatment of instability is a causal and cost effective therapy delaying the progression of osteoarthritis and minimising clinical symptoms. Performing both operations in one procedure facilitates early rehabilitation and return of these patients to the activities of daily living and sports.


Mitigating the heroin crisis in Baltimore, MD, USA: a cost-benefit analysis of a hypothetical supervised injection facility.
In Baltimore, MD, as in many cities throughout the USA, overdose rates are on the rise due to both the increase of prescription opioid abuse and that of fentanyl and other synthetic opioids in the drug market. Supervised injection facilities (SIFs) are a widely implemented public health intervention throughout the world, with 97 existing in 11 countries worldwide. Research has documented the public health, social, and economic benefits of SIFs, yet none exist in the USA. The purpose of this study is to model the health and financial costs and benefits of a hypothetical SIF in Baltimore. We estimate the benefits by utilizing local health data and data on the impact of existing SIFs in models for six outcomes: prevented human immunodeficiency virus transmission, Hepatitis C virus transmission, skin and soft-tissue infection, overdose mortality, and overdose-related medical care and increased medication-assisted treatment for opioid dependence. We predict that for an annual cost of $1.8 million, a single SIF would generate $7.8 million in savings, preventing 3.7 HIV infections, 21 Hepatitis C infections, 374 days in the hospital for skin and soft-tissue infection, 5.9 overdose deaths, 108 overdose-related ambulance calls, 78 emergency room visits, and 27 hospitalizations, while bringing 121 additional people into treatment. We conclude that a SIF would be both extremely cost-effective and a significant public health and economic benefit to Baltimore City.


Efficacy and safety of neoadjuvant FOLFIRINOX for borderline resectable pancreatic adenocarcinoma: improved efficacy compared with gemcitabine-based regimen.
Borderline resectable pancreatic cancer (BRPC) is a potentially resectable disease but is associated with poorer survival compared to primary resectable disease. There has been no prospective trial that compare the efficacy of FOLFIRNOX and gemcitabine-based regimen for BRPC. Between February 2013 and December 2014, 18 patients with BRPC receiving FOLFIRINOX were reviewed retrospectively. For comparative analysis, data for all BRPC patients (n=18) in our previous phase 2 study of neoadjuvant fixed-dose rate-gemcitabine plus capecitabine were pooled. Patients received a median 6 cycles (range, 3-13) of FOLFIRINOX. Surgical resection was performed in 12 patients (67%) and R0 resection in 9 patients. Median progression-free survival (PFS) and overall survival (OS) were 16.8 (95% confidence interval [CI], 9.4-24.2) and 21.2 (95% CI, 14.2-28.2) months, respectively. Patients who underwent surgical resection showed significantly better PFS (p=0.01) and OS (p=0.003) than those unresected. In the exploratory analysis, patients receiving FOLFIRINOX showed significantly longer PFS compared to those receiving fixed-dose rate-gemcitabine plus capecitabine (median 16.8 months [95% CI, 9.4-24.2] vs. 6.5 months [1.6-11.3]; p = 0.04). There was a trend toward improved OS in patients who received FOLFIRINOX (median 21.2 months [95% CI, 14.2-28.2]) compared to those who received fixed-dose rate-gemcitabine plus capecitabine (13.6 months [11.8-15.4]; p=0.12). FOLFIRINOX was feasible and effective as neoadjuvant chemotherapy for patients with BRPC and may have improved efficacy compared to a gemcitabine-based regimen.


Fluctuating magnetic field induced resonant activation.
In this paper, we have studied the properties of a Brownian particle at stationary state in the presence of a fluctuating magnetic field. Time dependence of the field makes the system thermodynamically open. As a signature of that the steady state distribution function becomes function of damping strength, intensity of fluctuations and constant parts of the applied magnetic field. It also depends on the correlation time of the fluctuating magnetic field. Our another observation is that the random magnetic field can induce the resonant activation phenomenon. Here correlation time is increased under the fixed variance of the fluctuating field. But if the correlation time (τ) increases under the fixed field strength then the mean first passage time rapidly grows at low τ and it almost converges at other limit. This is sharp contrast to the usual colored noise driven open system case where the mean first passage time diverges exponentially. We have also observed that a giant enhancement of barrier crossing rate occurs particularly at large strength of constant parts of the applied magnetic field even for very weak fluctuating magnetic field. Finally, break down of the Arrhenius result and disappearance of the Kramers' turn over phenomenon may occur in the presence of a fluctuating magnetic field.


Comparative study of humic acid removal and floc characteristics by electrocoagulation and chemical coagulation.
The current study aims at investigating the efficiency of electrocoagulation for the removal of humic acid from contaminated waters. In parallel, conventional chemical coagulation was conducted to asses humic acid removal patterns. The effect of varying contributing parameters (matrix pH, humic acid concentration, type of electrode (aluminum vs. iron), current density, solution conductivity, and distance between electrodes) was considered to optimize the electrocoagulation process for the best attainable humic acid removal efficiencies. Optimum removals were recorded at pH of 5.0-5.5, an electrical conductivity of 3000 μS/cm at 25 °C, and an electrode distance of 1 cm for both electrode types. With aluminum electrodes, a current density of 0.05 mA/cm2 outperformed 0.1 mA/cm2 yet not higher densities, whereas a current density of 0.8 mA/cm2 was needed for iron electrodes to exhibit comparable performance. With both electrode types, higher initial humic acid concentrations were removed at a slower rate but ultimately attained almost complete removals. On the other hand, the best humic acid removals (∼90%) by chemical coagulation were achieved at 4 mg/L for both coagulants. Also, higher removals were attained at elevated initial humic acid concentrations. Humic acid removals of 90% or higher at an initial HA concentration of 40 mg/L were exhibited, yet alum performed better at the highest experimented concentration. It was evident that iron flocs were larger, denser, and more geometrical in shape compared to aluminum flocs.


Regulation of white and opaque cell-type formation in Candida albicans by Rtt109 and Hst3.
How different cell types with the same genotype are formed and heritability maintained is a fundamental question in biology. We utilized white-opaque switching in Candida albicans as a system to study mechanisms of cell-type formation and maintenance. Each cell type has tractable characters, which are maintained over many cell divisions. Cell-type specification is under the control of interlocking transcriptional feedback loops, with Wor1 being the master regulator of the opaque cell type. Here we show that deletion of RTT109, encoding the acetyltransferase for histone H3K56, impairs stochastic and environmentally stimulated white-opaque switching. Ectopic expression of WOR1 mostly bypasses the requirement for RTT109, but opaque cells lacking RTT109 cannot be maintained. We have also discovered that nicotinamide induces opaque cell formation, and this activity of nicotinamide requires RTT109. Reducing the copy number of HST3, which encodes the H3K56 deacetylase, also leads to increased opaque formation. We further show that the Hst3 level is downregulated in the presence of genotoxins and ectopic expression of HST3 blocks genotoxin induced switching. This finding links genotoxin induced switching to Hst3 regulation. Together, these findings suggest RTT109 and HST3 genes play an important role in the regulation of white-opaque switching in C. albicans.


A mixed study systematic review of social media in nursing and midwifery education: Protocol.
To synthesize evidence on the use of social media in nursing and midwifery education. Social media is one type of online platform that is being explored to determine if there is value in using interactive, digital communication tools to support how nurses and midwives learn in a variety of settings. A sequential explanatory synthesis approach will be used for this mixed study review. Five bibliographic databases; PubMed, MEDLINE, CINAHL, Scopus, and ERIC will be searched using a combination of keywords relevant to social networking and social media, nursing and midwifery, and education. The search will not be limited by year of publication. Titles, abstracts, and full papers will be screened by two independent reviewers against inclusion and exclusion criteria, with any disagreements resolved via a third reviewer. Selected studies will undergo quality assessment and data extraction. Data synthesis will occur in three sequential phases, with quantitative and qualitative data analysed separately and then integrated where possible to provide a conceptual framework illustrating learning via social media. Funding for this review was confirmed in May 2016 by Sigma Theta Tau International and the National League for Nursing. The mixed study systematic review will produce the first rigorous synthesis on the use of social media in nursing and midwifery education and will have important implications for educators as well as students. It will also highlight knowledge gaps and make recommendations on the use of this novel technology in higher and continuing education.


Hepatocyte nuclear factor-3alpha binding at P sequences of the human growth hormone locus is associated with pituitary repressor function.
The human GH family consists of five genes, including the placental chorionic somatomammotropins (CS), within a single locus on chromosome 17. Based on nuclease sensitivity, the entire GH/CS locus is accessible in pituitary chromatin, yet only GH-N is expressed. Previously, we reported a P sequence element (263P) capable of repressing placental CS-A promoter activity in transfected pituitary (GC) cells, and our data indicated a possible role for nuclear factor-1 (NF-1) and regulatory factor X1 in this repression. In this study we show the formation of two independent pituitary complexes in vitro: a repressor complex containing NF-1 and a nonfunctional complex containing regulatory factor X1. In vitro repressor function is stabilized by the presence of P sequence element C (PSE-C), downstream of the previously characterized PSE-A and PSE-B. Repressor function is also dependent on an intact Pit-1 binding site in the CS-A promoter. EMSAs with PSE-C reveal binding of the hepatocyte nuclear factor-3/forkhead (HNF-3/fkh) family of transcription factors in rat pituitary GC cells. This observation is extended to human pituitary tissue, where HNF-3alpha's association with P sequences is confirmed by chromatin immunoprecipitation. Furthermore, protein-protein interactions between HNF-3alpha and NF-1 family members are demonstrated. These results identify HNF-3alpha as an additional member of the pituitary P sequence regulatory complex, implicating it in tissue-specific expression of the human GH/CS family.


Phase II trial of pegylated interferon and thalidomide in malignant metastatic melanoma.
Pegylated interferon and thalidomide demonstrate immunomodulatory and antiangiogenic activity, and efficacy in melanoma. The combination was evaluated in a phase II trial. Eligibility included biopsy-confirmed malignant melanoma with metastases and progression, maximum of two earlier systemic therapies, performance status of 0-2, and adequate hepatic, bone marrow and renal function. Pegylated interferon was administered at a dose of 0.5 microg/kg subcutaneously weekly and thalidomide 200 mg orally daily. Toxicity was evaluated every 2 weeks and response every 8 weeks. Eighteen patients were enrolled in this trial. Median age was 55.5 years (range: 29-80 years). Seventeen patients had visceral metastases and one had lymph node-only metastases. Two patients had brain metastases. Nine patients had received earlier adjuvant therapy and 16 patients had received earlier therapy for metastatic disease. Performance status was 0, 1 and 2 in 11, six and one patients, respectively. Severe (grade 4) toxicities observed were anemia in two patients and thrombocytopenia in one patient. No treatment-related deaths occurred. Dose escalation of thalidomide to 300 mg daily was feasible in four patients. One therapy-related hospitalization for nausea and dehydration occurred. No objective responses were noted; three patients demonstrated disease stabilization. The regimen of pegylated interferon and thalidomide was well tolerated. The combination, however, failed to demonstrate clinical efficacy in pretreated metastatic malignant melanoma.


Is the risk of HIV acquisition increased during and immediately after pregnancy? A secondary analysis of pooled HIV community-based studies from the ALPHA network.
Previous studies of HIV acquisition in pregnancy have been in specific population groups, such as sero-discordant couples which have shown an increased risk of HIV acquisition during pregnancy and studies of sexually active women where the results have been ambiguous. However these studies are unable to tell us what the overall impact of pregnancy is on HIV acquisition in the general population. Data from six community-based HIV cohorts were pooled to give 2,628 sero-conversions and a total of 178,000 person years of observation. Multiple imputation was used to allow for the uncertainty of exact sero-conversion date in surveillance intervals greater than the length of a pregnancy. Results were combined using Rubin's rules to give appropriate error bounds. The analysis was stratified into two periods: pre- and post- widespread availability of prevention of mother-to-child HIV transmission services. This allows us to assess whether there is reporting bias relating to a person's knowledge of their own HIV status which would become more widespread in the latter time period. Results suggest that women while pregnant have a lower risk of acquiring HIV infection over all periods (HRR 0.79, 95%CI 0.70-0.89) than women who were not pregnant. There is no evidence for a difference in the rate of HIV acquisition between postpartum and non-pregnant women (HRR 0.92 95%CI 0.84-1.03). Although there may be immunological reasons for increased risk of HIV acquisition during pregnancy, at a population level this study indicates a lower risk of HIV acquisition for pregnant women. Pregnant women may be more likely to be concordant with their current sexual partner than non-pregnant women, i.e. either already HIV positive prior to the pregnancy or if negative at the time of becoming pregnant more likely to have a negative partner.


Mechanisms of endothelial dysfunction: clinical significance and preventive non-pharmacological therapeutic strategies.
Endothelium-derived NO is not only a potent vasodilator but also inhibits platelet aggregation, vascular smooth muscle cell migration and proliferation, monocyte adhesion and adhesion molecule expression, thus protecting the vessel wall against the development of atherosclerosis. Cardiovascular risk factors are associated with an imbalance of the redox equilibrium towards oxidative stress and, therefore, impair the integrity of the endothelium, leading to endothelial activation which involves blunted endothelium-dependent vasodilation (vasodilator dysfunction) as well as inflammatory processes extending to the milieu within the whole vasculature, making plaques prone to rupture. In prospective studies endothelial dysfunction is associated with increased incidence of cardiovascular events. Thus, the prevention of endothelial dysfunction can determine a strong advantage in the clinical outcome of patients with cardiovascular risk factors. Several non-pharmacological interventions can prevent endothelial dysfunction or improve impaired endothelium-dependent vasodilation. Probably the most effective non-pharmacological measure is represented by aerobic physical activity, which can reduce production of oxidative stress associated to increasing age. Moreover, physical activity can improve endothelial dysfunction even in patients with cardiovascular risk factors such as essential hypertension. In addition several other approaches, including vitamin and fish oil supplementation, or tea and red wine consumption, can lead to an improvement of endothelium-dependent vasodilation, possibly by a restoration of NO availability. It is worth noting that most of non-pharmacological measures act by preventing or reducing oxidative stress.


Is new American Thyroid Association risk classification for hereditary medullary thyroid carcinoma applicable to Chinese patients? A single-center study.
The American Thyroid Association (ATA) proposed a new risk classification for hereditary medullary thyroid carcinoma (MTC) in 2015. This study aimed to assess whether the new guidelines are suitable for the Chinese population, and reported our experience on prophylactic thyroidectomy. A total of 73 patients from 22 families were screened as rearranged during transfection (RET) mutation carriers from 2010 to 2016 in Cancer Hospital, Chinese Academy of Medical Science; the medical history for each patient was collected. Based on the initial treatment, we identified the risk factors for poor prognosis by univariate and multivariate logistic regression. Then, 4 RET mutation carriers were enrolled for prophylactic thyroidectomy, and their pathological data and follow-up outcomes were recorded. In univariate and multivariate logistic regression analyses, age at initial surgery and risk classification were significant risk factors for stage III/IV hereditary MTC at initial diagnosis. The likelihood was increased by 11.6% per year of age at initial surgery [95% confidence interval (95% CI), 1.040-1.198; P=0.002). It was 7.888 times more likely to have III/IV stage disease for ATA highest risk patients, compared to ATA moderate risk individuals (95% CI, 1.607-38.717; P=0.003). Postoperative pathological results showed all 4 multiple endocrine neoplasia type 2A (MEN2A) patients had C-cell hyperplasia (CCH); multifocal malignancies were detected in 3 of them. All 4 patients were cured biochemically, and none developed permanent hypoparathyroidism. In Chinese individuals, hereditary MTC aggressiveness is in line with the new ATA risk classification. Germline RET gene mutation carriers should undergo prophylactic thyroidectomy according to basal serum calcitonin levels.


Congenital mid ureteral strictures.
Congenital mid ureteral stricture is rare. We report 7 cases, and discuss the differences in preoperative evaluation and surgical management compared to other obstructive entities. Medical records and imaging studies of 7 children identified with mid ureteral strictures between 1998 and 2002 were reviewed retrospectively. Five newborns presented with prenatal hydronephrosis, and 2 children presented at age 15 years, one in the course of evaluation of blunt trauma, and one due to pain and abdominal mass. Imaging studies included renal ultrasound, voiding cystourethrography, radionuclide renography and computerized tomography. All patients underwent retrograde pyelography. Pathological examination of each specimen was undertaken at the respective institutions. Prenatal hydronephrosis was the most common presentation. There were no urinary tract infections. All patients had significant obstruction on the affected side. No patient had vesicoureteral reflux. After imaging but before surgery the urinary obstruction was believed to be at the ureteropelvic junction in 4 patients and the ureterovesical junction in 2, and secondary to posterior urethral valves in 1. At cystoscopy all of the affected ureters had a normally located and normally configured orifice. Retrograde pyelography led to an accurate diagnosis of mid ureteral narrowing in all patients. Six patients underwent ureteroureterostomy, all of whom had satisfactory outcomes. In 1 of these patients contralateral nephrectomy was performed due to nonfunction of the multicystic dysplastic kidney. The remaining patient underwent nephrectomy for ipsilateral end stage kidney disease and hydronephrosis. In this patient the ureters were stenotic and suggested asymmetry in the thickness of the muscular coat, perhaps secondary to extrinsic compression. Congenital mid ureteral stricture is rare. Renal ultrasound and radionuclide renography alone do not reliably demonstrate the site of obstruction. Retrograde pyelography at the time of surgical correction of presumed ureteral obstruction is an important adjunct for correctly identifying the site of narrowing in the affected ureteral segment, unless the ureter has been imaged with another modality.


Mechanism of interferon action: simian virus 40-specific early polypeptides synthesized in untreated and interferon-treated monkey kidney cells.
The effect of interferon treatment on proteins synthesized in simian virus 40 (SV40)-infected cells in the presence of cytosine arabinoside was investigated. The following results were obtained: (i) In addition to previously described large tumor (T) antigen (94 kilodaltons) and small tumor (t) antigen (19 kilodaltons), a 62-kilodalton polypeptide was immunoprecipitated by SV40 anti-T antiserum from extracts of infected CV-1 and BSC-1 monkey kidney cells and transformed SV3T3 mouse cells. The 94-, 62-, and 19-kilodalton polypeptides were not precipitated with normal serum from extracts of infected cells, and they were not present in extracts of uninfected cells. (ii) The de novo synthesis of the 94-, 62-, and 19-kilodalton tumor antigens was inhibited in CV-1 and BSC-1 cells treated with interferon before infection; total cellular protein synthesis was not significantly affected by interferon treatment. The relative interferon sensitivity of the three polypeptides in lytically infected monkey cells was comparable; by contrast, interferon did not affect their synthesis in transformed mouse cells. (iii) The 62-kilodalton polypeptide was detected in monkey cells infected with the following strains of SV40: tsA30 at both 33 degrees C and 41 degrees C; wt 708, the parent of tsA30; dI 884; and wt 830, the parent of dI 884. The amount of the 62-kilodalton species relative to T antigen was significantly greater in tsA30-infected cells as compared to cells infected with other SV40 strains. (iv) T, t, and 62-kilodalton polypeptides were readily labeled with [(35)S]methionine during a 10-min pulse; in a subsequent chase, the (35)S-labeled 94-kilodalton T antigen was apparently converted to 89- and 84-kilodalton polypeptides but not to either the 62-kilodalton polypeptide species or t antigen. (v) Partial peptide maps suggest that the 62-kilodalton polypeptide and T antigen are closely related. (vi) In addition to the above described 62-kilodalton polypeptide, a 54-kilodalton polypeptide was also detected. However, the 54-kilodalton species appears to be of cellular origin because it was immunoprecipitated with both normal and anti-T antiserum from uninfected and lytically infected cells and from virally transformed cells.


A novel role of follistatin, an activin-binding protein, in the inhibition of activin action in rat pituitary cells. Endocytotic degradation of activin and its acceleration by follistatin associated with cell-surface heparan sulfate.
There are two types of the activin-binding protein follistatin (FS), FS-288 and FS-315. These result from alternative splicing of mRNA. FS-288 exhibits high affinity for cell-surface heparan sulfate proteoglycans, whereas FS-315 shows low affinity. To understand the physiological role of cell-associated FS, we investigated the binding of activin to cell-associated FS and its behavior on the cell surface using primary cultured rat pituitary cells. Affinity cross-linking experiments using 125I-activin A demonstrated that activin bound to rat pituitary cells via FS as well as to their receptors on the cell surface. FS-288 promoted the binding of activin A to the cell surface more markedly than FS-315. When the cells were incubated with 125I-activin A in the presence of FS-288, significant degradation of activin A was observed, and this was dependent on the FS-288 concentration. This activin degradation was abolished by heparan sulfate, chloroquine, and several lysosomal enzyme inhibitors. Moreover, FS-288 stimulated cellular uptake of activin A, whereas chloroquine suppressed lysosomal degradation following internalization, as demonstrated by microscopic autoradiography. These results suggest that cell-associated FS-288 accelerates the uptake of activin A into pituitary cells, leading to increased degradation by lysosomal enzymes, and thus plays a role in the activin clearance system.


Root phenotypes of dwarf and "overgrowth" SLN1 barley mutants, and implications for hypoxic stress tolerance.
Gibberellins are central to the regulation of plant development and growth. Action of gibberellins involves the degradation of DELLA proteins, which are negative regulators of growth. In barley (Hordeum vulgare), certain mutations affecting genes involved in gibberellin synthesis or coding for the barley DELLA protein (Sln1) confer dwarfism. Recent studies have identified new alleles of Sln1 with the capacity to revert the dwarf phenotype back to the taller phenotypes. While the effect of these overgrowth alleles on shoot phenotypes has been explored, no information is available for roots. Here, we examined aspects of the root phenotypes displayed by plants with various Sln1 gene alleles, and tested responses to growth in an O2-deficient root-zone as occurs during soil waterlogging. One overgrowth line, bearing the Sln1d.8 allele carrying two amino acid substitutions (one in the amino terminus and one in the GRAS domain of the encoded DELLA protein), displays profound and opposite effects on shoot height and root length. While it stimulates shoot height, it severely compromises root length by a reduction of cell size in zones distal to the root apex. In addition, Sln1d.8 plants counteract the negative effect of the original mutation on the formation of adventitious roots. Interestingly, plants bearing this allele display enhanced resistance to flooding stress in a way non-related with increased root porosity. Thus, various Sln1 gene alleles contribute to root phenotypes and can also influence plant responses to root-zone O2-deficiency stress.


COVID-19 Vaccination Knowledge and Attitude Among the General Population in Jeddah, Saudi Arabia.
Background The population's hesitancy to get the coronavirus disease 2019 (COVID-19) vaccination may pose a risk to public health worldwide. However, the causes and contributors to vaccine hesitancy in the Saudi people need to be understood. This study aimed to assess the knowledge and attitudes toward COVID-19 vaccination among the general population in Jeddah, Saudi Arabia. Methodology A cross-sectional study was conducted using an online structured questionnaire titled "Knowledge and attitude toward COVID-19 vaccination." The questionnaire collected demographic characteristics, knowledge, and attitudes toward COVID-19 vaccination among the general population in Jeddah, Saudi Arabia. The questionnaire was distributed through links on various sites, including Twitter and WhatsApp. Results A total of 544 participants were included in the present study. Overall, 64.9% were males, and 35.1% were females. Most of the population had received three doses (83.6%) of the COVID-19 vaccine. About half of the participants had a university education (56.8%), 17.5% of respondents were postgraduates, and 14.2% had secondary education. Overall, 41.4% of the population had a low knowledge level, and 58.5% had a low attitude toward COVID-19 vaccination. Receiving the COVID-19 vaccine was significantly (p < 0.05) associated with the population's knowledge and attitude toward COVID-19 vaccination. In addition, the education level substantially affected the knowledge and attitude toward COVID-19 vaccination. Additionally, knowledge of COVID-19 vaccination had a significant correlation (p < 0.05) with the attitude toward the vaccine. Conclusions Despite the high prevalence of the population who received the three doses of the COVID-19 vaccine in Jeddah city, the study showed insufficient knowledge and attitude among the population toward COVID-19 vaccination. However, fortunately, education plays an essential role in improving the knowledge of COVID-19 vaccination.


Promoting Bike Helmet Safety for Urban Children Through a Culturally Tailored Educational Video Intervention.
Bicycle-related falls are a significant cause of mortality and morbidity. Use of bicycle helmets substantially reduces risk of severe traumatic brain injury but compliance with this safety practice is particularly low in urban children. We recruited eleven 8- to 15-year-old youth to participate in focus groups to inform the creation of a video promoting helmet use. Key emerging themes included that youth were responsible for keeping themselves safe and that most youth had cell phones with cases to protect them. A video was created that linked the concept of use of cases to protect phones to use of helmets to protect heads. Soliciting information from urban youth was helpful for developing this educational video.


[Progress in research and prenatal diagnosis for ring chromosomes].
Genetic counseling for ring chromosomes, particularly hereditary ring chromosomes, is still difficult. In recent years, molecular biology has provided more clues for the genetic mechanism of ring chromosomes. In this paper, the epidemiology, pathogenesis, clinical phenotype and prenatal diagnosis of ring chromosomes are reviewed.


[Abscess of the kidney. Apropos of 21 cases].
Renal abscess is rather an uncommon lesion caused predominantly by an urogenic infection. The authors report 21 cases in a period of 10 years. They describe and evaluate the actual investigation possibilities which are accurate enough to lead to the right diagnosis of renal abscess in a good rate. The evolution of the therapeutic modes is studied, with a special reference to the percutaneous drainage which is to substitute the classical surgery of this abscess. For the authors, treated in the right time and in the right way, renal abscess is nowadays a benign lesion, preserving a good prognosis for the kidney and the patient.


Effects of Different Conditioning Activities on 100-m Dash Performance in High School Track and Field Athletes.
This study compared the effects of different conditioning activities on the 100-m dash performance of 11 male, high school track and field athletes (mean age = 16.3; SD = 1.2 years). Participants performed a 100-m dash seven minutes after each of four randomized conditioning protocols, with each condition and 100-m dash separated by 3-10 days. The conditioning protocols were (a) control, no conditioning activity; (b) weighted plyometric, three sets of 10 repetitions of alternate leg bounding with additional load of 10% of the body mass; (c) free sprint, two 20-m sprints; and (d) resisted sprint (RS), two 20-m resisted sprints using an elastic tubing tool. We obtained session ratings of perceived exertion (SRPE) immediately after each conditioning protocol. There were no significant differences between any of the three experimental conditioning activities on 100-m sprint time, but the RS protocol improved 100-m sprint time compared with the control (no conditioning) protocol ( p < .001). The RS also led to greater sprint velocity and higher SRPE compared with the control condition ( p < .01). There was no significant association between SRPE and 100-m performance ( p = .77, r = .05). These results suggest a benefit for young male track and field athletes to the elastic tubing warm-up activities prior to the 100-m dash.


High-resolution ultrasonography in detection and follow-up of a tumour of the forearm. Case report.
A 39-year-old man had a mass in his right flexor medial mid-forearm of unknown aetiology for two years. Preoperative high-resolution ultrasonography showed a well-defined solid mass with reduced echogenicity. The mass was excised and histopathological examination showed neurilemmoma. There had been no recurrence of the tumour six months after operation.


Diagnosis and treatment of joint tuberculosis.
Tuberculosis of the joints is not a clinical oddity and a diagnosis of tuberculous infection must be considered in all joint lesions if diagnosis is to be made early. A history of insidious onset of pain, especially if accompanied by pulmonary symptoms or a history of contact with a tuberculous person, should alert the clinician to the possibility of this diagnosis. The tuberculin test, roentgenograms, culture of aspirated fluids and biopsy, by anthrotomy or punch, continue to be the standard procedures for establishing the diagnosis. The differential diagnosis must include the entire gamut of bone and joint disease. Chemotherapy combining streptomycin and dihydrostreptomycin with isonicotinic acid hydrazid and para-aminosalicylic acid is of extreme value in the eradication of draining sinuses and in the advancement of the ideal surgical date; but general physical and mental hygiene, rest and the prevention or correction of deformities is a continuing therapeutic necessity. Fusion of the affected area is advocated in almost all lesions although there is some hope that functioning joints may be preserved with early diagnosis, conservative surgical treatment and more efficient antibiotics. A postoperative regime similar to the preoperative treatment must be continued until the stabilization is firm or until there is no evidence of activity.


The W.A.I.O.T. Definition of Peri-Prosthetic Joint Infection: A Multi-center, Retrospective Validation Study.
Peri-prosthetic joint infection (PJI) definition plays an important role in diagnostic and therapeutic decisions. However, while several criteria have been proposed by eminent institutions to define a PJI in the last decade, their clinical validation has been rarely performed. Aim of the present multicenter, international, retrospective study was to validate the World Association against Infection in Orthopedics and Trauma (WAIOT) pre/intra-operative PJI definition with post-operative confirmatory tests. A total of 210 patients, undergoing hip (n = 86) or knee (n = 124) revision surgery for any reason in six orthopedic centers in Africa, Asia, Europe and South America, were retrospectively evaluated at a two years minimum follow-up after surgery. All the available pre-, intra- and post-operative findings were collected and analyzed according to the WAIOT criteria, which include a set of tests to confirm (Rule In) or to exclude (Rule Out) a PJI. On average, patients were investigated pre/intra-operatively with 3.1 ± 1.1 rule out and 2.7 ± 0.9 rule in tests; the presence of a fistula or exposed implant was reported in 37 patients (17.6%). According to pre/intraoperative findings, 36.2% of the patients were defined as affected by high-grade PJI (n = 76; average score: 2.3 ± 0.8), 21.9% by low-grade PJI (n = 46; average score: 0.8 ± 0.8), 10.5% by biofilm-related implant malfunction (n = 22; average score: -1.6 ± 0.8), 2.9% as contamination (n = 6; average score: -3.5 ± 1.0), and 28.6% as no infection (n = 60; average score: -3.0 ± 1.4). Pre/intra-operative PJI definitions matched post-operative confirmatory tests, in 97.1% of the patients. This is, to our knowledge, one of the largest study ever conducted to validate a PJI definition The retrospective analysis in different centers was greatly facilitated by the structure of the WAIOT definition, that allows to include different tests on the basis of their sensitivity/specificity, while the comparison between pre/intra-operative and post-operative findings offered the internal validation of the scoring system. Our results authenticate the WAIOT definition as a reliable, simple tool to identify patients affected by PJI prior to joint revision surgery.


Methods for pooled analyses of epidemiologic studies.
This paper presents a systematic methodology for the pooling and analysis of previously conducted epidemiologic studies. It discusses the methodologic issues to consider and the procedures to follow when conducting a pooled analysis of individual subject level data. I review random and fixed effects models to estimate pooled risks and the methods to examine whether heterogeneity in study-specific effect estimates exists. Analytic strategies presented here can be used to assess sources of heterogeneity, particularly those originating from different study designs and methods. I describe methods for incorporating a qualitative assessment of the study design and data collection methods into the quantitative estimation of the overall effect. Finally, I make recommendations for future pooled analyses of epidemiologic studies.


Update on targeted therapies for advanced non-small cell lung cancer: nivolumab in context.
While the initial treatment of non-small cell lung cancer (NSCLC) usually relies on surgical resection followed by systemic cytotoxic chemotherapy and/or radiation therapy, recent advances in understanding of NSCLC biology and immunology have spurred the development of numerous targeted therapies. In particular, a class of immune modulatory drugs targeting the immune checkpoint pathways has demonstrated remarkable durable remissions in a select minority of advanced NSCLC patients, potentially heralding the elusive "cancer cure". This review focuses on the clinical evidence for one of these agents, nivolumab, and clarifies the role of this drug in the context of the other targeted therapies currently available for the treatment of NSCLC. We also discuss the impact of nivolumab on patient quality of life and health economics.


Female sperm storage mediates post-copulatory costs and benefits of ejaculate anticipatory plasticity in the guppy.
Males of many species evolved the capability of adjusting their ejaculate phenotype in response to social cues to match the expected mating conditions. When females store sperm for a prolonged time, the expected fitness return of plastic adjustments of ejaculate phenotype may depend on the interval between mating and fertilization. Although prolonged female sperm storage (FSS) increases the opportunity for sperm competition, as a consequence of the longer temporal overlap of ejaculates from several males, it may also create variable selective forces on ejaculate phenotype, for example by exposing trade-offs between sperm velocity and sperm survival. We evaluated the relationship between the plasticity of ejaculate quality and FSS in the guppy, Poecilia reticulata, a polyandrous live-bearing fish in which females store sperm for several months and where stored sperm contribute significantly to a male's lifelong reproductive success. In this species, males respond to the perception of future mating opportunities by increasing the quantity (number) and quality (swimming velocity) of ready-to-use sperm (an anticipatory response called 'sperm priming'). Here we investigated (a) the effect of sperm priming on in vitro sperm viability at stripping and its temporal decline (as an estimate of sperm survival), and (b) the in vivo competitive fertilization success in relation to female sperm storage using artificial insemination. As expected, sperm-primed males produced more numerous and faster sperm, but with a reduced in vitro sperm viability at stripping and after 4 hr, compared with their counterparts. Artificial insemination revealed that the small (nonsignificant) advantage of primed sperm when fertilization immediately follows insemination is reversed when eggs are fertilized by female-stored sperm, weeks after insemination. By suggesting a plastic trade-off between sperm velocity and viability, these results demonstrate that prolonged female sperm storage generates divergent selection pressures on ejaculate phenotype.


Advances in the treatment of pancreatic cancer.
Conventional pancreatic resections have proved unsatisfactory in the treatment of pancreatic cancer. A new operative approach that includes resection of the pancreas en bloc with the regional nodes and pertinent vascular structures has been developed. The procedure was carried out in 27 patients, the majority of whom had advanced neoplasms. The two-year actuarial survival of those who escaped complications of the procedure and lived was 46%. The technical details, postoperative problems, and the benefits of this operation are discussed.


Direct Adaptive Preassigned Finite-Time Control With Time-Delay and Quantized Input Using Neural Network.
This paper investigates an adaptive finite-time control (FTC) problem for a class of strict-feedback nonlinear systems with both time-delays and quantized input from a new point of view. First, a new concept, called preassigned finite-time performance function (PFTF), is defined. Then, another novel notion, called practically preassigned finite-time stability (PPFTS), is introduced. With PFTF and PPFTS in hand, a novel sufficient condition of the FTC is given by using the neural network (NN) control and direct adaptive backstepping technique, which is different from the existing results. In addition, a modified barrier function is first introduced in this work. Moreover, this work is first to focus on the FTC for the situation that the time-delay and quantized input simultaneously exist in the nonlinear systems. Finally, simulation results are carried out to illustrate the effectiveness of the proposed scheme.


Thermal proteome profiling identifies the membrane-bound purinergic receptor P2X4 as a target of the autophagy inhibitor indophagolin.
Signaling pathways are frequently activated through signal-receiving membrane proteins, and the discovery of small molecules targeting these receptors may yield insights into their biology. However, due to their intrinsic properties, membrane protein targets often cannot be identified by means of established approaches, in particular affinity-based proteomics, calling for the exploration of new methods. Here, we report the identification of indophagolin as representative member of an indoline-based class of autophagy inhibitors through a target-agnostic phenotypic assay. Thermal proteome profiling and subsequent biochemical validation identified the purinergic receptor P2X4 as a target of indophagolin, and subsequent investigations suggest that indophagolin targets further purinergic receptors. These results demonstrate that thermal proteome profiling may enable the de novo identification of membrane-bound receptors as cellular targets of bioactive small molecules.


Cell-Free PURE System: Evolution and Achievements.
The cell-free protein synthesis (CFPS) system, as a technical core of synthetic biology, can simulate the transcription and translation process in an in vitro open environment without a complete living cell. It has been widely used in basic and applied research fields because of its advanced engineering features in flexibility and controllability. Compared to a typical crude extract-based CFPS system, due to defined and customizable components and lacking protein-degrading enzymes, the protein synthesis using recombinant elements (PURE) system draws great attention. This review first discusses the elemental composition of the PURE system. Then, the design and preparation of functional proteins for the PURE system, especially the critical ribosome, were examined. Furthermore, we trace the evolving development of the PURE system in versatile areas, including prototyping, synthesis of unnatural proteins, peptides and complex proteins, and biosensors. Finally, as a state-of-the-art engineering strategy, this review analyzes the opportunities and challenges faced by the PURE system in future scientific research and diverse applications.


Human immunosuppressive factors produced by T cell hybridoma.
A Human OKT8-positive T cell hybridoma was established by using concanavalin A (ConA)-activated peripheral blood mononuclear cells (PBMC) fused with CEM-AGR cells. A culture supernatant of the established T cell hybridoma HI4.2D6 inhibited the mitogen induced proliferation of peripheral blood mononuclear cells (PBMC). It inhibited IL-1-, IL-2, or IL-3-dependent proliferation of each factor-dependent mouse cell lines. While the inhibitory activity of IL-1-induced proliferation was stable, that of IL-2- and IL-3-induced proliferation was abrogated within a week at 4 degrees C. Inhibition of IL-2-dependent growth was also observed using human IL-2-dependent cells, but the growth of other factor-independent human hematopoietic cell lines was not affected at all. By gel filtration, the activity inhibiting IL-2- or IL-3-dependent proliferation was found in the fractions with approximate molecular weight of 18,000 and 100,000.


Nitrogen balance of healthy Dutch women before and during pregnancy.
Experimental studies including longitudinal nitrogen balance studies could provide insight into protein metabolism in pregnancy. Our aim was to determine the development of nitrogen balance during pregnancy compared with nitrogen balance before pregnancy in women consuming imposed constant diets. We also tracked changes in muscle mass and lean body mass by measuring urinary 3-methylhistidine (3-MeH) and urinary creatinine. Nitrogen balance was determined over 8 d in 12 healthy Dutch women before pregnancy and at weeks 12, 23, and 34 of gestation. Complete daily diets were supplied during each balance period so that each subject's energy, protein, and macronutrient intakes were similar in amount and composition in all 4 balance periods. Throughout pregnancy there was no significant change in loss of nitrogen in feces and therefore no change in protein digestibility. The amount of nitrogen excreted in urine in late pregnancy (11.0 +/- 1.4 g/d) was significantly (P < 0.01) less than in early pregnancy (12.6 +/- 1.3 g/d). Nitrogen retention increased toward term, even though energy balance became progressively negative. The difference between the first (-0.4 +/- 1.7 g N/d) and third (1.2 +/- 1.6 g N/d) trimester was significant (P < 0.05). No differences were found in either 3-MeH or creatinine excretion between trimesters. These urinary nitrogen excretion and nitrogen retention data show that when the dietary supply remains constant, nitrogen balance increases toward the end of pregnancy, suggesting a more efficient use of dietary protein later in pregnancy. Urinary 3-MeH and creatinine excretion indicated no change in protein metabolism.


Structure characterization and immunocompetence of a glucan from the fruiting bodies of Cantharellus cibarius.
A protein-bound polysaccharide fraction (JBP-1) was obtained from the fruiting bodies of Cantharellus cibarius. Its chemical composition was studied by the cooperative usage of multiple chemical and spectral methods and characterized to be a fraction with a molecular weight of 4.8 × 10(5) Da and only composed of glucose. Methylation analysis revealed that the sugar residues in JBP-1 are existing as t-, 1,6-, and 1,3,6-linked Glcp sugar residues. The immunocompetence of the fraction was evaluated with the proliferation assay of mouse splenocytes, and the result revealed that JBP-1 could significantly stimulate the proliferation of mouse splenocytes in a dose-dependent manner, with p < 0.001 at the concentration of 100 μg/ml and 30 μg/ml, p < 0.05 at 10 μg/ml. These results give us a primary scientific evidence to further explore the pharmaceutical function of this mushroom.


Announcement: World Water Day - March 22, 2017.
World Water Day is sponsored by the United Nations and observed each year on March 22. This year, World Water Day focuses on wastewater, which includes sewage, storm water, and discarded water used in the community (1). Many developing countries have inadequate wastewater management strategies because they lack resources, infrastructure, available technology, or space. Untreated wastewater in these countries is often disposed of directly into rivers, lakes, or oceans, polluting the environment and increasing the risk for disease transmission (2).


Interactive effects of pesticide exposure and habitat structure on behavior and predation of a marine larval fish.
Coastal development has generated multiple stressors in marine and estuarine ecosystems, including habitat degradation and pollutant exposure, but the effects of these stressors on the ecology of fishes remain poorly understood. We studied the separate and combined effects of an acute 4 h sublethal exposure of the pyrethroid pesticide esfenvalerate and structural habitat complexity on behavior and predation risk of larval topsmelt (Atherinops affinis). Larvae were exposed to four nominal esfenvalerate concentrations (control, 0.12, 0.59, 1.18 μg/L), before placement into 12 L mesocosms with a three-spine stickleback (Gasterosteus aculeatus) predator. Five treatments of artificial eelgrass included a (1) uniform and (2) patchy distribution of eelgrass at a low density (500 shoots per m(2)), a (3) uniform and (4) patchy distribution of eelgrass at a high density (1,000 shoots per m(2)), and (5) the absence of eelgrass. The capture success of predators and aggregative behavior of prey were observed in each mesocosm for 10 min of each trial, and mortality of prey was recorded after 60 min. Exposure to esfenvalerate increased the proportion of larvae with swimming abnormalities. Surprisingly, prey mortality did not increase linearly with pesticide exposure but increased with habitat structure (density of eelgrass), which may have been a consequence of compensating predator behavior. The degree of prey aggregation decreased with both habitat structure and pesticide exposure, suggesting that anti-predator behaviors by prey may have been hampered by the interactive effects of both of these factors.


Cancer Diagnosis Epigenomics Scientific Workflow Scheduling in the Cloud Computing Environment Using an Improved PSO Algorithm
Objective: Epigenetic modifications involving DNA methylation and histone statud are responsible for the stable maintenance of cellular phenotypes. Abnormalities may be causally involved in cancer development and therefore could have diagnostic potential. The field of epigenomics refers to all epigenetic modifications implicated in control of gene expression, with a focus on better understanding of human biology in both normal and pathological states. Epigenomics scientific workflow is essentially a data processing pipeline to automate the execution of various genome sequencing operations or tasks. Cloud platform is a popular computing platform for deploying large scale epigenomics scientific workflow. Its dynamic environment provides various resources to scientific users on a pay-per-use billing model. Scheduling epigenomics scientific workflow tasks is a complicated problem in cloud platform. We here focused on application of an improved particle swam optimization (IPSO) algorithm for this purpose. Methods: The IPSO algorithm was applied to find suitable resources and allocate epigenomics tasks so that the total cost was minimized for detection of epigenetic abnormalities of potential application for cancer diagnosis. Result: The results showed that IPSO based task to resource mapping reduced total cost by 6.83 percent as compared to the traditional PSO algorithm. Conclusion: The results for various cancer diagnosis tasks showed that IPSO based task to resource mapping can achieve better costs when compared to PSO based mapping for epigenomics scientific application workflow.


Comparing single and multiple imputation strategies for harmonizing substance use data across HIV-related cohort studies.
Although standardized measures to assess substance use are available, most studies use variations of these measures making it challenging to harmonize data across studies. The aim of this study was to evaluate the performance of different strategies to impute missing substance use data that may result as part of data harmonization procedures. We used self-reported substance use data collected between August 2014 and June 2019 from 528 participants with 2,389 study visits in a cohort study of substance use and HIV. We selected a low (heroin), medium (methamphetamine), and high (cannabis) prevalence drug and set 10-50% of each substance to missing. The data amputation mimicked missingness that results from harmonization of disparate measures. We conducted Monte Carlo simulations to evaluate the comparative performance of single and multiple imputation (MI) methods using the relative mean bias, root mean square error (RMSE), and coverage probability of the 95% confidence interval for each imputed estimate. Without imputation (i.e., listwise deletion), estimates of substance use were biased, especially for low prevalence outcomes such as heroin. For instance, even when 10% of data were missing, the complete case analysis underestimated the prevalence of heroin by 33%. MI, even with as few as five imputations produced the least biased estimates, however, for a high prevalence outcome such as cannabis with low to moderate missingness, performance of single imputation strategies improved. For instance, in the case of cannabis, with 10% missingness, single imputation with regression performed just as well as multiple imputation resulting in minimal bias (relative mean bias of 0.06% and 0.07% respectively) and comparable performance (RMSE = 0.0102 for both and coverage of 95.8% and 96.2% respectively). Our results from imputation of missing substance use data resulting from data harmonization indicate that MI provided the best performance across a range of conditions. Additionally, single imputation for substance use data performed comparably under scenarios where the prevalence of the outcome was high and missingness was low. These findings provide a practical application for the evaluation of several imputation strategies and helps to address missing data problem when combining data from individual studies.


dictyExpress: a web-based platform for sequence data management and analytics in Dictyostelium and beyond.
Dictyostelium discoideum, a soil-dwelling social amoeba, is a model for the study of numerous biological processes. Research in the field has benefited mightily from the adoption of next-generation sequencing for genomics and transcriptomics. Dictyostelium biologists now face the widespread challenges of analyzing and exploring high dimensional data sets to generate hypotheses and discovering novel insights. We present dictyExpress (2.0), a web application designed for exploratory analysis of gene expression data, as well as data from related experiments such as Chromatin Immunoprecipitation sequencing (ChIP-Seq). The application features visualization modules that include time course expression profiles, clustering, gene ontology enrichment analysis, differential expression analysis and comparison of experiments. All visualizations are interactive and interconnected, such that the selection of genes in one module propagates instantly to visualizations in other modules. dictyExpress currently stores the data from over 800 Dictyostelium experiments and is embedded within a general-purpose software framework for management of next-generation sequencing data. dictyExpress allows users to explore their data in a broader context by reciprocal linking with dictyBase-a repository of Dictyostelium genomic data. In addition, we introduce a companion application called GenBoard, an intuitive graphic user interface for data management and bioinformatics analysis. dictyExpress and GenBoard enable broad adoption of next generation sequencing based inquiries by the Dictyostelium research community. Labs without the means to undertake deep sequencing projects can mine the data available to the public. The entire information flow, from raw sequence data to hypothesis testing, can be accomplished in an efficient workspace. The software framework is generalizable and represents a useful approach for any research community. To encourage more wide usage, the backend is open-source, available for extension and further development by bioinformaticians and data scientists.


Clinical features of the neutropenic host: definitions and initial evaluation.
Initial evaluation of patients with febrile neutropenia includes a thorough history and physical examination; a complete blood cell count; measurement of serum creatinine, blood urea nitrogen, transaminases, and C-reactive protein; and culture of blood (samples from a peripheral vein and/or catheter). Chest radiography is indicated for patients with respiratory signs or symptoms. Signs and symptoms of inflammation may be minimal or absent. However, a search should be undertaken in the sites most commonly infected, including the periodontium, pharynx, lower esophagus, lung, perineum, eyes, and skin. Blood samples, including samples from catheter lumen(s), if present, and a peripheral vein, should be obtained for cultures for bacteria and fungi. Urine culture is indicated in the presence of signs or symptoms of urinary tract infection, a urinary catheter in place, or abnormal results of urinalysis. Fever is defined as a single axillary temperature measurement of > or =37.5 degrees C (oral temperature of > or =38.0 degrees C). Neutropenia is defined as a neutrophil count of <1000 cells/mm3.


Designing polymers for cartilage uptake: effects of architecture and molar mass.
Osteoarthritis (OA) is a progressive disease, involving the progressive breakdown of cartilage, as well as changes to the synovium and bone. There are currently no disease-modifying treatments available clinically. An increasing understanding of the disease pathophysiology is leading to new potential therapeutics, but improved approaches are needed to deliver these drugs, particularly to cartilage tissue, which is avascular and contains a dense matrix of collagens and negatively charged aggrecan proteoglycans. Cationic delivery vehicles have been shown to effectively penetrate cartilage, but these studies have thus far largely focused on proteins or nanoparticles, and the effects of macromolecular architectures have not yet been explored. Described here is the synthesis of a small library of polycations composed of N-(2-hydroxypropyl)methacrylamide (HPMA) and N-(3-aminopropyl)methacrylamide (APMA) with linear, 4-arm, or 8-arm structures and varying degrees of polymerization (DP) by reversible addition fragmentation chain-transfer (RAFT) polymerization. Uptake and retention of the polycations in bovine articular cartilage was assessed. While all polycations penetrated cartilage, uptake and retention generally increased with DP before decreasing for the highest DP. In addition, uptake and retention were higher for the linear polycations compared to the 4-arm and 8-arm polycations. In general, the polycations were well tolerated by bovine chondrocytes, but the highest DP polycations imparted greater cytotoxicity. Overall, this study reveals that linear polymer architectures may be more favorable for binding to the cartilage matrix and that the DP can be tuned to maximize uptake while minimizing cytotoxicity.


Comparing alternative and traditional dissemination metrics in medical education.
The impact of academic scholarship has traditionally been measured using citation-based metrics. However, citations may not be the only measure of impact. In recent years, other platforms (e.g. Twitter) have provided new tools for promoting scholarship to both academic and non-academic audiences. Alternative metrics (altmetrics) can capture non-traditional dissemination data such as attention generated on social media platforms. The aims of this exploratory study were to characterise the relationships among altmetrics, access counts and citations in an international and pre-eminent medical education journal, and to clarify the roles of these metrics in assessing the impact of medical education academic scholarship. A database study was performed (September 2015) for all papers published in Medical Education in 2012 (n = 236) and 2013 (n = 246). Citation, altmetric and access (HTML views and PDF downloads) data were obtained from Scopus, the Altmetric Bookmarklet tool and the journal Medical Education, respectively. Pearson coefficients (r-values) between metrics of interest were then determined. Twitter and Mendeley (an academic bibliography tool) were the only altmetric-tracked platforms frequently (> 50%) utilised in the dissemination of articles. Altmetric scores (composite measures of all online attention) were driven by Twitter mentions. For short and full-length articles in 2012 and 2013, both access counts and citation counts were most strongly correlated with one another, as well as with Mendeley downloads. By comparison, Twitter metrics and altmetric scores demonstrated weak to moderate correlations with both access and citation counts. Whereas most altmetrics showed limited correlations with readership (access counts) and impact (citations), Mendeley downloads correlated strongly with both readership and impact indices for articles published in the journal Medical Education and may therefore have potential use that is complementary to that of citations in assessment of the impact of medical education scholarship.


NKG2D signaling regulates IL-17A-producing γδT cells in mice to promote cancer progression.
γδT cells are unconventional T cells particularly abundant in mucosal tissues that play an important role in tissue surveillance, homeostasis, and cancer. γδT cells recognize stressed cells or cancer cells through the NKG2D receptor to kill these cells and maintain normality. Contrary to the well-established anti-tumor function of these NKG2D-expressing γδT cells, we show here that, in mice, NKG2D regulates a population of pro-tumor γδT cells capable of producing IL-17A. Germline deletion of Klrk1, the gene encoding NKG2D, reduced the frequency of γδT cells in the tumor microenvironment and delayed tumor progression. We further show that blocking NKG2D reduced the capability of γδT cells to produce IL-17A in the pre-metastatic lung and that co-culture of lung T cells with NKG2D ligand-expressing tumor cells specifically increased the frequency of γδT cells. Together, these data support the hypothesis that, in a tumor microenvironment where NKG2D ligands are constitutively expressed, γδT cells accumulate in an NKG2D-dependent manner and drive tumor progression by secreting pro-inflammatory cytokines, such as IL-17A.


Particles containing RNA-instructed DNA polymerase and virus-related RNA in human breast cancers.
Human breast cancers contain an RNA related to that of mouse mammary tumor virus. In 79% of the breast malignancies examined, this type of RNA is a 70S-component encapsulated with RNA-instructed DNA polymerase in a particle possessing the density characteristics of RNA tumor viruses. Further, the DNA synthesized by the human RNA enzyme complex hybridizes specifically with the RNA of mouse mammary tumor virus. Thus, four features diagnostic of agents similar to mouse mammary tumor virus are also exhibited by a particle found with high frequency in human breast cancers. The accumulating evidence for the involvement of RNA tumor viruses in at least some human neoplasias is becoming increasingly compelling.


Environmentally adaptive processing for shallow ocean applications: A sequential Bayesian approach.
The shallow ocean is a changing environment primarily due to temperature variations in its upper layers directly affecting sound propagation throughout. The need to develop processors capable of tracking these changes implies a stochastic as well as an environmentally adaptive design. Bayesian techniques have evolved to enable a class of processors capable of performing in such an uncertain, nonstationary (varying statistics), non-Gaussian, variable shallow ocean environment. A solution to this problem is addressed by developing a sequential Bayesian processor capable of providing a joint solution to the modal function tracking and environmental adaptivity problem. Here, the focus is on the development of both a particle filter and an unscented Kalman filter capable of providing reasonable performance for this problem. These processors are applied to hydrophone measurements obtained from a vertical array. The adaptivity problem is attacked by allowing the modal coefficients and/or wavenumbers to be jointly estimated from the noisy measurement data along with tracking of the modal functions while simultaneously enhancing the noisy pressure-field measurements.


Molecular and cytogenetic analysis of a familial microdeletion of Xq.
Cytogenetic analysis of a male infant referred for poor neurological development and failure to thrive showed a microdeletion of the X chromosome, his karyotype being 46,Y,del(X)(pter----q21.1:: q21.2----qter). His mother and grandmother were also found to carry the deletion. DNA probes were used to define the deletion molecularly and it was shown to span intervals 2 to 6 of Cremers et al, a portion of Xq that contains the TCD gene and genes whose absence is associated with deafness and mental retardation. RFLP analysis together with X inactivation studies using the probe M27 beta verified the carrier status of the female relatives and showed non-random X inactivation in the heterozygous females.


[Determination of dichloromethane and trichloromethane residues in ranitidine hydrochloride by headspace liquid phase microextraction coupled with gas chromatography].
A method for the determination of residual dichloromethane and trichloromethane in ranitidine hydrochloride by headspace liquid phase microextraction coupled with gas chromatography (GC) was developed. A homemade device was used to protect the organic drop. The effects of the nature of extraction solvent, extraction time, extraction temperature and microdrop volume on the extraction efficiency were investigated separately. The optimal experimental conditions were as follows: 2 microL of n-tridecane as extraction solvent, 30 min of extraction time, 60 degrees C of extraction temperature. The correlation coefficients of linear calibration curve were 0.9733 and 0.9724 within the concentration ranges of dichloromethane (1-10 microg/g) and trichloromethane (1-10 microg/g), respectively. The detection limits of dichlormethane and trichloromethane were 0.0273 microg/g and 0.0410 microg/g, respectively, the relative standard deviations were lower than 4.36% and 5.89%, and the recoveries of the method were 93.6%-102% and 98.1% respectively. The method is simple and reliable.


Caffeine in tea plants [Camellia sinensis (L) O. Kuntze]: in situ lowering by Bacillus licheniformis (Weigmann) Chester.
Tea plants (Camellia sinensis) contain 5-6% caffeine that is responsible for the stimulating effect of the beverage. As the tolerance to caffeine varies among individuals, low caffeine tea would be an ideal alternative. While assessing the potential of a few selected bacteria-Bacillus licheniformis, B. subtilis and B. firmus, to multiply on nutrient medium supplemented with glucose (5%) and tea leaf extract (2%), it was observed that only B. licheniformis could proliferate on this medium. Hence, B. licheniformis was used for further studies. Tea plants were sprayed with a suspension of B. licheniformis at a dilution of 5 x 10(8) CFU/ml containing 0.1% Tween 80 as surfactant. In situ lowering of caffeine from tea leaves was evident without affecting the quality of the other tea components. Further, there was no change in the morphological and physiological characteristics as well. It is suggested that spraying of B. licheniformis may be useful in yielding decaffeinated tea with good flavour and aroma.


Slippage of Newtonian liquids: influence on the dynamics of dewetting thin films.
Slippage of Newtonian liquids in the presence of a solid substrate is a newly found phenomenon, the origin of which is still under debate. In this article, we present a new analysis method to extract the slip length. Enhancing the slip of liquids is an important issue for microfluidic devices that demand for high throughput at low pumping power. We study the velocity of short-chained liquid polystyrene (PS) films dewetting from nonwettable solid substrates. We show how the dynamics of dewetting is influenced by slippage, and we compare the results of two types of substrates that give rise to different slip lengths. As substrates, Si wafers that have been coated with octadecyltrichlorosilane (OTS) or dodecyltrichlorosilane (DTS) were used. Our results demonstrate that the dewetting velocity for PS films on DTS is significantly larger than on OTS and that this difference originates from the different slip lengths of the liquid on top of the two surfaces. For PS films of thickness between 130 and 230 nm, we find slip lengths between 400 nm and 6 microm, depending on substrate and temperature.


Temporally distinct phosphorylations differentiate Tau-dependent learning deficits and premature mortality in Drosophila.
Abnormally phosphorylated Tau protein, the major component of neurofibrillary tangles, is critical in the pathogenesis of Alzheimer's disease and related Tauopathies. We used Drosophila to examine the role of key disease-associated phosphorylation sites on Tau-mediated neurotoxicity. We present evidence that the late-appearing phosphorylation on Ser(238) rather than hyperphosphorylation per se is essential for Tau toxicity underlying premature mortality in adult flies. This site is also occupied at the time of neurodegeneration onset in a mouse Tauopathy model and in damaged brain areas of confirmed Tauopathy patients, suggesting a similar critical role on Tau toxicity in humans. In contrast, occupation of Ser(262) is necessary for Tau-dependent learning deficits in adult Drosophila. Significantly, occupation of Ser(262) precedes and is required for Ser(238) phosphorylation, and these temporally distinct phosphorylations likely reflect conformational changes. Because sequential occupation of Ser(262) and Ser(238) is required for the progression from Tau-mediated learning deficits to premature mortality in Drosophila, they may also play similar roles in the escalating symptom severity in Tauopathy patients, congruent with their presence in damaged regions of their brains.


Genetic and Ultrastructural Analysis Reveals the Key Players and Initial Steps of Bacterial Magnetosome Membrane Biogenesis.
Magnetosomes of magnetotactic bacteria contain well-ordered nanocrystals for magnetic navigation and have recently emerged as the most sophisticated model system to study the formation of membrane bounded organelles in prokaryotes. Magnetosome biosynthesis is thought to begin with the formation of a dedicated compartment, the magnetosome membrane (MM), in which the biosynthesis of a magnetic mineral is strictly controlled. While the biomineralization of magnetosomes and their subsequent assembly into linear chains recently have become increasingly well studied, the molecular mechanisms and early stages involved in MM formation remained poorly understood. In the Alphaproteobacterium Magnetospirillum gryphiswaldense, approximately 30 genes were found to control magnetosome biosynthesis. By cryo-electron tomography of several key mutant strains we identified the gene complement controlling MM formation in this model organism. Whereas the putative magnetosomal iron transporter MamB was most crucial for the process and caused the most severe MM phenotype upon elimination, MamM, MamQ and MamL were also required for the formation of wild-type-like MMs. A subset of seven genes (mamLQBIEMO) combined within a synthetic operon was sufficient to restore the formation of intracellular membranes in the absence of other genes from the key mamAB operon. Tracking of de novo magnetosome membrane formation by genetic induction revealed that magnetosomes originate from unspecific cytoplasmic membrane locations before alignment into coherent chains. Our results indicate that no single factor alone is essential for MM formation, which instead is orchestrated by the cumulative action of several magnetosome proteins.


LBL assembly of Ag@Ti3C2TXand chitosan on PLLA substrate to enhance antibacterial and biocompatibility.
Poly L-lactic acid (PLLA) is a non-toxic, biocompatible degradable polymer material with excellent mechanical properties after moulding. However, it faces challenges in the use of biomedical materials because of its intolerance to bacteria. Here, we use an easy-to-operate method to prepare a composite multilayer membrane: PLLA membrane was used as substrates to assemble positively charged chitosan and negatively charged Ag@MXene on the surface using the layer-by-layer (LBL) method. The assembly process was detected by fluorescein isothiocyanate-labelled chitosan and the thickness of the coating multilayer was also detected as 210.0 ± 12.1 nm for P-M membrane and 460.5 ± 26.5 nm for P-Ag@M membrane. The surface self-assembled multilayers exhibited 91.27% and 96.11% growth inhibition ratio againstEscherichia coliandStaphylococcus aureusstrains under 808 nm near-infrared laser radiation with a synergistic photothermal antibacterial effect. Furthermore, best biocompatibility of P-M and P-Ag@M membranes compare to PLLA membrane motivated us to further explore its application in biomedical materials.


Formation of an Isolable Divinylborinium Ion through Twofold 1,2-Carboboration between a Diarylborinium Ion and Diphenylacetylene.
Borinium ions, that is, two-coordinate boron cations, are the most electron-deficient isolable boron compounds. As borinium ions have only four formal valence electrons on boron, they should show a strong tendency to accept electron pairs on the boron atom to fill its valence shell. Thus chemical reactions of borinium ions are expected to give products in which the coordination number of boron is increased from two to three or four. However, contrary to this expectation, we found that the dimesitylborinium ion (Mes2 B+ ) undergoes twofold 1,2-carboboration reactions with two equivalents of diphenylacetylene to yield an unprecedented borinium ion (1+ ) with two substituted vinyl groups on the boron center. NMR spectroscopy and X-ray diffraction analysis of 1+ , together with electronic-structure calculations, revealed that the positive charge is delocalized over the entire π-conjugated system. The fact that the chemical transformation of a borinium ion gives rise to a different borinium ion without a change in the coordination number is remarkable and should provide new insight into the chemistry of the Group 13 elements.


Lipogenesis from amino acids in perfused isolated dog skin.
Lipogenesis from amino acids has been studied in isolated perfused dog skin. Uniformly labeled alanine-(14)C, glycine-(14)C, isoleucine-(14)C, leucine-(14)C, phenylalanine-(14)C, and valine-(14)C are all incorporated into the cutaneous lipids, with significant incorporation into most of the isolated lipid fractions. Efficiency of lipogenesis has been expressed relative to the extent of incorporation of acetate under the same experimental conditions. This efficiency was highest for the three branched-chain amino acids. The accuracy, uses, and limitations of the perfusion technique for the study of cutaneous lipogenesis have been evaluated.


Less is More: Evidence-Based Management of Bronchiolitis.
Bronchiolitis is a common cause of outpatient visits and hospitalization in children younger than age 2 years. Despite the frequency with which pediatricians manage this diagnosis, there is significant variability in care in both the inpatient and outpatient setting. This may be due in part to changing guidelines set forth by leading pediatric organizations such as the American Academy of Pediatrics, as increasing evidence emerges that traditional therapies are not effective. This article reviews current evidence-based practices for diagnosis and treatment of bronchiolitis, and provides an overview of inpatient management. [Pediatr Ann. 2017;46(7):e252-e256.].


The Recombination Hotspot Paradox: Co-evolution between PRDM9 and its target sites.
Recombination often concentrates in small regions called recombination hotspots where recombination is much higher than the genome's average. In many vertebrates, including humans, gene PRDM9 specifies which DNA motifs will be the target for breaks that initiate recombination, ultimately determining the location of recombination hotspots. Because the sequence that breaks (allowing recombination) is converted into the sequence that does not break (preventing recombination), the latter sequence is over-transmitted to future generations and recombination hotspots are self-destructive. Given their self-destructive nature, recombination hotspots should eventually become extinct in genomes where they are found. While empirical evidence shows that individual hotspots do become inactive over time (die), hotspots are abundant in many vertebrates: a contradiction called the Recombination Hotspot Paradox. What saves recombination hotspots from their foretold extinction? Here we formulate a co-evolutionary model of the interaction among sequence-specific gene conversion, fertility selection, and recurrent mutation. We find that allelic frequencies oscillate leading to stable limit cycles. From a biological perspective this means that when fertility selection is weaker than gene conversion, it cannot stop individual hotspots from dying but can save them from extinction by driving their re-activation (resuscitation). In our model, mutation balances death and resuscitation of hotspots, thus maintaining their number over evolutionary time. Interestingly, we find that multiple alleles result in oscillations that are chaotic and multiple targets in oscillations that are asynchronous between targets thus helping to maintain the average genomic recombination probability constant. Furthermore, we find that the level of expression of PRDM9 should control for the fraction of targets that are hotspots and the overall temperature of the genome. Therefore, our co-evolutionary model improves our understanding of how hotspots may be replaced, thus contributing to solve the Recombination Hotspot Paradox. From a more applied perspective our work provides testable predictions regarding the relation between mutation probability and fertility selection with life expectancy of hotspots.