An Italian cost-effectiveness analysis of paclitaxel albumin (nab-paclitaxel) + gemcitabine vs gemcitabine alone for metastatic pancreatic cancer patients: the APICE study.

PubMed

Lazzaro, Carlo; Barone, Carlo; Caprioni, Francesco; Cascinu, Stefano; Falcone, Alfredo; Maiello, Evaristo; Milella, Michele; Pinto, Carmine; Reni, Michele; Tortora, Giampaolo

2018-04-20

the APICE study evaluates the cost-effectiveness of nanoparticle albumin-bound paclitaxel (nab-paclitaxel - Nab-P) + gemcitabine (G) vs G alone in metastatic pancreatic cancer (MPC) from the Italian National Health Service (INHS) standpoint. A 4-year, 4 health states (progression-free; progressed; end of life; death) Markov model based on the MPACT trial was developed to estimate costs (Euro [€], 2017 values), and quality-adjusted life years (QALYs). Patients were assumed to receive intravenously Nab-P 125 mg/m 2  + G 1000 mg/m 2 on days 1, 8, and 15 every 4 weeks or G alone 1000 mg/m 2 weekly for 7 out of 8 weeks (cycle 1) and then on days 1, 8, and 15 every 4 weeks (cycle 2 and subsequent cycles) until progression. One-way and probabilistic sensitivity analyses explored the uncertainty surrounding the baseline incremental cost-utility ratio (ICUR). Nab-P + G totals 0.154 incremental QALYs and €7082.68 incremental costs vs G alone. ICUR (€46,021.58) is lower than the informal threshold value of €87,330 adopted by the Italian Medicines Agency during 2010-2013 for reimbursing oncological drugs. Sensitivity analyses confirmed the robustness of the baseline findings. Nab-P + G in MPC patients can be considered cost-effective for the INHS.

Nab-paclitaxel-associated photosensitivity: report in a woman with non-small cell lung cancer and review of taxane-related photodermatoses.

PubMed

Beutler, Bryce D; Cohen, Philip R

2015-04-01

Taxanes [paclitaxel, nab-paclitaxel (Abraxane, Celgene Corp, USA), and docetaxel]-used in the treatment of lung, breast, and head and neck cancers-have been associated with cutaneous adverse effects, including photodermatoses. We describe a woman with non-small cell lung cancer who developed a photodistributed dermatitis associated with her nab-paclitaxel therapy and review photodermatoses in patients receiving taxanes. The features of a woman with a nab-paclitaxel-associated photodistributed dermatitis are presented and the literature on nab-paclitaxel-associated photosensitivity is reviewed. Our patient developed nab-paclitaxel-associated photodistributed dermatitis on the sun-exposed surfaces of her upper extremities, which was exacerbated with each course of nab-paclitaxel. Biopsies revealed an interface dermatitis and laboratory studies were negative for lupus erythematosus and dermatomyositis. Her condition improved following topical corticosteroid cream application and strict avoidance of sunlight. Chemotherapy can be associated with adverse mucocutaneous events, including dermatoses on sun-exposed areas of the skin. Paclitaxel and nab-paclitaxel have both been associated with photodermatoses, including dermatitis, erythema multiforme, onycholysis, and subacute cutaneous lupus erythematosus. Strict avoidance of sun exposure, topical or oral corticosteroids, and/or discontinuation of the drug results in improvement with progressive resolution of symptoms and skin lesions. Development of photodermatoses is not an absolute contraindication to continuing chemotherapy, provided that the cutaneous condition resolves with dermatosis-directed treatment and the patient avoids sun exposure.

Peritoneal metastasis as a predictive factor for nab-paclitaxel in patients with pretreated advanced gastric cancer: an exploratory analysis of the phase III ABSOLUTE trial.

PubMed

Takashima, Atsuo; Shitara, Kohei; Fujitani, Kazumasa; Koeda, Keisuke; Hara, Hiroki; Nakayama, Norisuke; Hironaka, Shuichi; Nishikawa, Kazuhiro; Kimura, Yutaka; Amagai, Kenji; Fujii, Hirofumi; Muro, Kei; Esaki, Taito; Choda, Yasuhiro; Takano, Toshimi; Chin, Keisho; Sato, Atsushi; Goto, Masahiro; Fukushima, Norimasa; Hara, Takuo; Machida, Nozomu; Ohta, Manabu; Boku, Narikazu; Shimura, Masashi; Morita, Satoshi; Koizumi, Wasaburo

2018-05-31

In the ABSOLUTE trial, weekly nanoparticle albumin-bound paclitaxel (w-nab-PTX) showed non-inferiority to weekly solvent-based paclitaxel (w-sb-PTX) for overall survival (OS). Thus, w-nab-PTX might be an option for second-line chemotherapy in advanced gastric cancer (AGC). However, predictive factors for efficacies of these agents have not been evaluated. Patients previously enrolled in the ABSOLUTE trial were divided into apparent peritoneal metastasis group (PM group) and no apparent peritoneal metastasis group (no PM group) based on baseline imaging evaluated by RECIST ver. 1.1 criteria and amount of ascites. OS, progression-free survival, and overall response rate were compared between two arms in each group. This study included 240 and 243 patients in the w-nab-PTX and w-sb-PTX arms, respectively. In the PM group, the w-nab-PTX arm (n = 88) had longer OS than the w-sb-PTX arm (n = 103), and median survival time (MST) of 9.9 and 8.7 months [hazard ratio (HR) 0.63; 95% CI 0.45-0.88; P = 0.0060], respectively. In the no PM group, the w-nab-PTX arm (n = 140) had shorter OS than the w-sb-PTX arm (n = 152), and MST of 11.6 and 15.7 months (HR 1.40; 95% CI 1.06-1.86; P = 0.0180), respectively. After adjusting for prognostic factors, the HR for OS in the w-nab-PTX arm versus the w-sb-PTX arm was 0.59 (95% CI 0.42-0.83; P = 0.0023; PM group) and 1.34 (95% CI 1.01-1.78; P = 0.0414; no PM group), with significant interaction between treatment efficacy and presence of peritoneal metastasis (P = 0.0003). The presence of apparent peritoneal metastasis might be a predictive factor for selecting w-nab-PTX for pretreated AGC patients. JapicCTI-132059.

PAR-CLIP data indicate that Nrd1-Nab3-dependent transcription termination regulates expression of hundreds of protein coding genes in yeast

PubMed Central

2014-01-01

Background Nrd1 and Nab3 are essential sequence-specific yeast RNA binding proteins that function as a heterodimer in the processing and degradation of diverse classes of RNAs. These proteins also regulate several mRNA coding genes; however, it remains unclear exactly what percentage of the mRNA component of the transcriptome these proteins control. To address this question, we used the pyCRAC software package developed in our laboratory to analyze CRAC and PAR-CLIP data for Nrd1-Nab3-RNA interactions. Results We generated high-resolution maps of Nrd1-Nab3-RNA interactions, from which we have uncovered hundreds of new Nrd1-Nab3 mRNA targets, representing between 20 and 30% of protein-coding transcripts. Although Nrd1 and Nab3 showed a preference for binding near 5′ ends of relatively short transcripts, they bound transcripts throughout coding sequences and 3′ UTRs. Moreover, our data for Nrd1-Nab3 binding to 3′ UTRs was consistent with a role for these proteins in the termination of transcription. Our data also support a tight integration of Nrd1-Nab3 with the nutrient response pathway. Finally, we provide experimental evidence for some of our predictions, using northern blot and RT-PCR assays. Conclusions Collectively, our data support the notion that Nrd1 and Nab3 function is tightly integrated with the nutrient response and indicate a role for these proteins in the regulation of many mRNA coding genes. Further, we provide evidence to support the hypothesis that Nrd1-Nab3 represents a failsafe termination mechanism in instances of readthrough transcription. PMID:24393166

Comparison of treatment patterns and economic outcomes among metastatic pancreatic cancer patients initiated on nab-paclitaxel plus gemcitabine versus FOLFIRINOX.

PubMed

McBride, Ali; Bonafede, Machaon; Cai, Qian; Princic, Nicole; Tran, Oth; Pelletier, Corey; Parisi, Monika; Patel, Manish

2017-10-01

The economic burden of metastatic pancreatic cancer (mPC) is substantial while treatment options are limited. Little is known about the treatment patterns and healthcare costs among mPC patients who initiated first-line gemcitabine plus nanoparticle albumin-bound paclitaxel (nab-P + G) and FOLFIRINOX. The MarketScan® claims databases were used to identify adults with ≥2 claims for pancreatic cancer, 1 claim for a secondary malignancy, completed ≥1 cycle of nab-P + G or FOLFIRINOX during 4/1/2013 and 3/31/2015, and had continuous plan enrollment for ≥6 months pre- and 3 months after the first-line treatment. Duration of therapy, per patient per month (PPPM) costs of total healthcare, mPC-related treatment, and supportive care were measured during first-line therapy. 550 mPC patients met selection criteria (nab-P + G, n = 294; FOLFIRINOX, n = 256). There was no difference in duration of therapy (p = 0.60) between nab-P + G and FOLFIRINOX. Compared with FOLFIRINOX, patients with nab-P + G had higher chemotherapy drug costs but lower treatment administration costs and supportive care costs (all p < 0.01). Patients treated with nab-P + G (vs FOLFIRINOX) had similar treatment duration but lower costs of outpatient prescriptions, treatment administration and supportive care. Lower supportive care costs in the nab-P + G cohort were mainly driven by lower utilization of pegfilgrastim and anti-emetics.

Clinicopathological differences between variants of the NAB2-STAT6 fusion gene in solitary fibrous tumors of the meninges and extra-central nervous system.

PubMed

Nakada, Satoko; Minato, Hiroshi; Nojima, Takayuki

2016-07-01

Investigations on the NAB2-STAT6 fusion gene in solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs) have increased since its discovery in 2013. Although several SFTs reported without NAB2-STAT6 fusion gene analysis, we reviewed 546 SFTs/HPCs with NAB2-STAT6 fusion gene analysis in this study and investigated differences between the gene variants. In total, 452 cases tested positive for the NAB2-STAT6 fusion gene, with more than 40 variants being detected. The most frequent of these were NAB2 exon 6-STAT6 exon 16/17/18 and NAB2 exon 4-STAT6 exon 2/3, with the former occurring most frequently in SFTs in meninges, soft tissues, and head and neck; the latter predominated in SFTs in the pleura and lung. There was no difference between the histology of SFTs and fusion gene variants. A follow-up analysis of SFTs showed that 51 of 202 cases had a recurrence, with 18 of 53 meningeal SFTs having a local recurrence and/or metastasis within 0-19 years. In meninges and soft tissue, SFTs with the NAB2 exon 6-STAT6 exon 16/17/18 tended to recur more frequently than SFTs with the NAB2 exon 4-STAT6 exon 2/3. Clinicopathological data, including yearly follow-ups, are required for meningeal SFTs/HPCs to define the correlation of variants of NAB2-STAT6 fusion gene.

[Nab-Paclitaxel plus Gemcitabine Hydrochloride in Patients with Metastatic or Recurrent Pancreatic Cancer - A Single Institution Experience].

PubMed

Takeda, Yutaka; Katsura, Yoshiteru; Ohmura, Yoshiaki; Sakamoto, Takuya; Akiyama, Yasuki; Kuwahara, Ryuichi; Morimoto, Yoshihiro; Ishida, Tomo; Oneda, Yasuo; Murakami, Kouhei; Naito, Atsushi; Kagawa, Yoshinori; Takeno, Atsushi; Kato, Takeshi; Tamura, Shigeyuki

2016-11-01

Pancreatic adenocarcinoma is one of the leading causes of cancer deaths in Japan.Albumin -bound paclitaxel (nab-paclitaxel)plus gemcitabine hydrochloride(GEM)combination chemotherapy provided significant improvements in the overall and progression-free survival in a phase III trial in Europe and America and a phase II trial in Japan.As a result, this combination therapy was approved for use in Japan. We evaluated the efficacy of nab-paclitaxel plus GEM with metastatic or recurrent pancreatic cancer.Between December 2014 and March 2016, 11 patients received nab-paclitaxel plus GEM as follows: nab-paclitaxel(125mg/m2 of body-surface area)followed by GEM(1,000mg/m2)on days 1, 8, and 15 every 4 weeks.The treatment was continued until disease progression, unacceptable adverse events, discontinuation as decided by the investigators, or patient refusal. The mean age was 65.6 years(range, 48-75 years), and 8 out of 11 patients were men.Ten patients had an Eastern Cooperative Oncology Group(ECOG)performance status(PS)of 0.Ten patients had metastatic disease.Only 4 patients had no prior therapy.The mean duration of treatment was 10.2 weeks(range, 2-41 weeks).The relative dose intensities of nab-paclitaxel and GEM were 90.6%(66.7-100%)and 87.5%(62.9-100%), respectively.The major Grade 3 or 4 hematological toxicities were leucopenia(54.5%), neutropenia(36.4%), anemia (27.3%), and thrombocytopenia(18.2%).The major grade 2 or 3 non-hematological toxicities were fatigue(45.6%), skin rash(27.3%), peripheral sensory neuropathy(9.1%), anorexia(9.1%), and stomatitis(9.1%).There were no treatmentrelated deaths.Interstitial lung disease was not observed.The 6 month progression-free and overall survival rate were 25.7% and 66.7%, respectively. The disease control rate was 90.9%(complete response, n=0; partial response, n=1; stable disease, n=9; progressive disease, n=1). Nab-paclitaxel plus GEM is well tolerated and associated with efficacy and improved survival outcomes.Nab -paclitaxel

NAB2-STAT6 fusion gene analysis in two cases of meningeal solitary fibrous tumor/hemangiopericytoma with late distant metastases.

PubMed

Nakada, Satoko; Minato, Hiroshi; Takegami, Tsutomu; Kurose, Nozomu; Ikeda, Hiroko; Kobayashi, Masako; Sasagawa, Yasuo; Akai, Takuya; Kato, Takashi; Yamamoto, Norio; Nojima, Takayuki

2015-10-01

We present two cases of meningeal solitary fibrous tumor (SFT)/hemangiopericytoma (HPC) with immunohistochemistry of STAT6 and analysis of NAB2-STAT6 fusion genes. Case 1 was a 37-year-old male with a left middle fossa tumor; case 2 was a 68-year-old female with a cerebellar tumor. They showed late metastasis to the lung or bone 8 or 13 years, respectively, after the first surgery. Histology of both primary and metastatic tumors showed a cellular hemangiopericytomatous pattern with nuclear atypia. The primary tumors showed nuclear staining of STAT6, but both metastatic tumors showed nuclear and cytoplasmic STAT6. DNA sequencing revealed two kinds of NAB2-STAT6 fusion genes. One consisted of exon 6 of NAB2, intron 6 of NAB2, and the middle of exon 17 of STAT6 (observed in the primary and metastatic tumors of case 1); the other consisted of exon 6 of NAB2 and the beginning of exon 17 of STAT6 (observed in the metastatic tumor of case 2). The primary tumor of case 2 had both fusion genes. To the best of our knowledge, we are the first to report NAB2-STAT6 fusion gene analysis in primary and metastatic meningeal SFT/HPCs and a case showed different fusion gene status in the metastatic tumor.

[A Case of Shock Due to nabPTX Administration Successfully Treated with Cytokine Adsorption Therapy].

PubMed

Yoshikawa, Katsuhiro; Yamamoto, Daigo; Tsubota, Yu; Sueoka, Noriko; Chiba, Tsukuru; Ishizuka, Mariko; Kon, Masanori

2017-11-01

The patient was a 71-year-old woman with ER(+), PgR(-), HER2(3+), and Ki-674 2% breast cancer. After surgery for left breast cancer(Bt+Ax), epirubicin, cyclophosphamide therapy was administered as postoperative adjuvant chemotherapy, and nabPTX plus trastuzumab therapy was started sequentially. The patient was hospitalized due to severe neutrope- nia(neutrophils 0/mm3)from nabPTX, but her condition stabilized after admission. However, the patient suddenly went into shock after 3 days and was thus transferred to the ICU. Her general condition was rapidly improved through cytokine adsorption therapy in the ICU. After 5 days, she was extubated and wheeled back to a general ward. She was discharged without problems in the succeeding months. In this case, FN or cardiovascular diseases was ruled out, and engraftment syndrome was considered given that cytokine adsorption therapy significantly improved the patient's condition. Considering the risk for severe neutropenia in nabPTX administration, clinicians should exercise caution when administering the drug.

Inversion-mediated gene fusions involving NAB2-STAT6 in an unusual malignant meningioma.

PubMed

Gao, F; Ling, C; Shi, L; Commins, D; Zada, G; Mack, W J; Wang, K

2013-08-20

Meningiomas are the most common primary intracranial tumours, with ∼3% meeting current histopathologic criteria for malignancy. In this study, we explored the transcriptome of meningiomas using RNA-Seq. Inversion-mediated fusions between two adjacent genes, NAB2 and STAT6, were detected in one malignant tumour, creating two novel in-frame transcripts that were validated by RT-PCR and Sanger sequencing. Gene fusions of NAB2-STAT6 were recently implicated in the pathogenesis of solitary fibrous tumours; our study suggested that similar fusions may also have a role in a malignant meningioma with unusual histopathologic features.

Meningeal hemangiopericytoma and solitary fibrous tumors carry the NAB2-STAT6 fusion and can be diagnosed by nuclear expression of STAT6 protein.

PubMed

Schweizer, Leonille; Koelsche, Christian; Sahm, Felix; Piro, Rosario M; Capper, David; Reuss, David E; Pusch, Stefan; Habel, Antje; Meyer, Jochen; Göck, Tanja; Jones, David T W; Mawrin, Christian; Schittenhelm, Jens; Becker, Albert; Heim, Stephanie; Simon, Matthias; Herold-Mende, Christel; Mechtersheimer, Gunhild; Paulus, Werner; König, Rainer; Wiestler, Otmar D; Pfister, Stefan M; von Deimling, Andreas

2013-05-01

Non-central nervous system hemangiopericytoma (HPC) and solitary fibrous tumor (SFT) are considered by pathologists as two variants of a single tumor entity now subsumed under the entity SFT. Recent detection of frequent NAB2-STAT6 fusions in both, HPC and SFT, provided additional support for this view. On the other hand, current neuropathological practice still distinguishes between HPC and SFT. The present study set out to identify genes involved in the formation of meningeal HPC. We performed exome sequencing and detected the NAB2-STAT6 fusion in DNA of 8/10 meningeal HPC thereby providing evidence of close relationship of these tumors with peripheral SFT. Due to the considerable effort required for exome sequencing, we sought to explore surrogate markers for the NAB2-STAT6 fusion protein. We adopted the Duolink proximity ligation assay and demonstrated the presence of NAB2-STAT6 fusion protein in 17/17 HPC and the absence in 15/15 meningiomas. More practical, presence of the NAB2-STAT6 fusion protein resulted in a strong nuclear signal in STAT6 immunohistochemistry. The nuclear reallocation of STAT6 was detected in 35/37 meningeal HPC and 25/25 meningeal SFT but not in 87 meningiomas representing the most important differential diagnosis. Tissues not harboring the NAB2-STAT6 fusion protein presented with nuclear expression of NAB2 and cytoplasmic expression of STAT6 proteins. In conclusion, we provide strong evidence for meningeal HPC and SFT to constitute variants of a single entity which is defined by NAB2-STAT6 fusion. In addition, we demonstrate that this fusion can be rapidly detected by STAT6 immunohistochemistry which shows a consistent nuclear reallocation. This immunohistochemical assay may prove valuable for the differentiation of HPC and SFT from other mesenchymal neoplasms.

A Phase Ib study of ruxolitinib + gemcitabine ± nab-paclitaxel in patients with advanced solid tumors.

PubMed

Bauer, Todd M; Patel, Manish R; Forero-Torres, Andres; George, Thomas J; Assad, Albert; Du, Yining; Hurwitz, Herbert

2018-01-01

Aberrant activation of the Janus-associated kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is associated with increased malignant cell proliferation and survival. This Phase Ib study evaluated ruxolitinib, a potent JAK1/2 inhibitor, in combination with gemcitabine with or without nab-paclitaxel in patients with advanced solid tumors. Patients received ruxolitinib + gemcitabine (regimen A) or ruxolitinib + gemcitabine + nab-paclitaxel (regimen B). The objective of the dose-finding phase was to identify the maximum tolerated doses (MTDs) of ruxolitinib plus gemcitabine with or without nab-paclitaxel. Among 42 patients enrolled, the median age was 62.5 years, 81.0% had pancreatic cancer, and almost 62% had received prior systemic therapy. Regimen A was tolerated with standard doses of gemcitabine; regimen B was tolerated with reduced doses of gemcitabine/nab-paclitaxel or concomitant granulocyte colony-stimulating factor. The sponsor decided to terminate the study early due to the interim analysis results of the Phase III JANUS 1 study. Discontinuations were mainly due to radiologic or clinical disease progression (81.0% of patients). Median treatment durations were 55.5 days (cohort A0) and 150.5 days (pooled B cohorts). Four patients (pooled B cohorts) had dose-limiting toxicities: grade 3 pneumonia (n=1), grade 4 neutropenia (n=1), and grade 4 thrombocytopenia (n=2). The most common grade 3/4 hematologic adverse events (AEs) were anemia, thrombocytopenia, and neutropenia. Serious AEs occurring in ≥2 patients in cohort A0 or pooled B cohorts were abdominal pain, sepsis (cohort A0), dehydration, anemia, and asthenia (pooled B cohorts). Overall response rates (ORRs) were 12.5% in cohort A0 and 38.5% in pooled B cohorts. Among patients with pancreatic cancer, ORR was 23.5% (14.0% cohort A0 30.0% pooled B cohorts). The study was terminated early prior to reaching MTDs per sponsor decision; although ruxolitinib plus gemcitabine with or

Nutrient dynamics in streams and the role of J-NABS

Treesearch

Patrick J. Mulholland; Jackson R. Webster

2010-01-01

Nutrient dynamics in streams has been an important topic of research since the 1960s. Here we review this topic and the significant role played by J-NABS in its development. We limit this review almost exclusively to studies of N and P because these elements have been shown to limit productivity in streams. We use the expression nutrient dynamics for studies that...

Effects of dietary benzoic acid and sodium-benzoate on performance, nitrogen and mineral balance and hippuric acid excretion of piglets.

PubMed

Gräber, Tobias; Kluge, Holger; Hirche, Frank; Broz, Jirí; Stangl, Gabriele I

2012-06-01

The objective of this study was to compare the effects of sodium-benzoate (NaB) with those of benzoic acid (BAc) on growth performance of piglets as well as nutrient digestibility, nitrogen and mineral balance, urinary pH, and the urinary excretion of BAc and hippuric acid (HAc). The study was conducted with 120 weaning piglets (6.5 kg body weight), divided in four groups (15 replicates of two piglets each), which received (1) a basal diet (Control), or the basal diet supplemented with (2) 4 g NaB per kg (Group 4NaB), (3) 3.5 g BAc per kg (Group 3.5BAc) or (4) 5 g BAc per kg (Group 5BAc). Performance data were monitored over a 42-day period. Urine and faeces were collected from day 28-33 in metabolic cages with five piglets per treatment. Piglets of Groups 3.5BAc and 5BAc had similarly a considerably improved average daily gain and feed intake (p < 0.05). Performance of Group 4NaB was not significantly different from the other groups. Compared to the Control, the nitrogen retention was only improved in Group 5BAc (p < 0.05); the other groups showed intermediate values. In the supplemented groups, most of the BAc was excreted as HAc in urine, but only Groups 3.5BAc and 5BAc had reduced urinary pH (p < 0.05). Daily intake and faecal and urinary excretion of P and Ca were not affected by the treatment. The molar excess of Na in Group 4NaB was reflected by higher renal excretion of Na compared to the other groups (p < 0.05).

Metastatic melanoma cells with BRAF G469A mutation: nab-paclitaxel better than vemurafenib?

PubMed

Porcelli, Letizia; Guida, Gabriella; Tommasi, Stefania; Guida, Michele; Azzariti, Amalia

2015-08-01

BRAF G469A is a missense mutation within exon 11 of the BRAF gene resulting in a constitutively activated enzyme frequently associated with MAP kinase cascade signaling activation. No evidence currently exists about its role in determining sensitivity/resistance to BRAF inhibitors, utilized in the treatment of patients carrying BRAF V600 mutations, and to chemotherapy. The newly established metastatic melanoma (MM) cell line MO-1 was characterized for its sensitivity to vemurafenib and nab-paclitaxel, both already utilized for the treatment of MM. All analyses were carried out by comparing results with those found in MM cells wild type for BRAF or mutated in V600. In addition, cellular effectors were investigated by ELISA kits, western blotting and flow cytometry. The exposure to vemurafenib inhibited MO-1 cell proliferation at concentrations similar to those obtained in vemurafenib-resistant melanoma models, and an explanation of this sensitivity is the strong activation of Erk1/2 and the low expression of MITF. Nab-paclitaxel strongly reduced proliferation of MO-1 cells perhaps for the very low expression level of PMEL17, transcriptionally regulated by MITF and negatively involved in determining sensitivity to taxanes. Thus, the mutation BRAF G469A in MM might be related to a weak effectiveness of therapy with BRAF inhibitors and a promising therapeutic approach may be with nab-paclitaxel.

Crystal Structure of human Karyopherin β2 bound to the PY-NLS of Saccharomyces cerevisiae Nab2

PubMed Central

Soniat, Michael; Sampathkumar, Parthasarathy; Collett, Garen; Gizzi, Anthony S.; Banu, Radhika N.; Bhosle, Rahul C.; Chamala, Swetha; Chowdhury, Sukanya; Fiser, Andras; Glenn, Alan S.; Hammonds, James; Hillerich, Brandan; Khafizov, Kamil; Love, James D.; Matikainen, Bridget; Seidel, Ronald D.; Toro, Rafael; Kumar, P. Rajesh; Bonanno, Jeffery B.; Chook, Yuh Min; Almo, Steven C.

2013-01-01

Import-Karyopherin or Importin proteins bind nuclear localization signals (NLSs) to mediate the import of proteins into the cell nucleus. Karyopherin β2 or Kapβ2, also known as Transportin, is a member of this transporter family responsible for the import of numerous RNA binding proteins. Kapβ2 recognizes a targeting signal termed the PY-NLS that lies within its cargos to target them through the nuclear pore complex. The recognition of PY-NLS by Kapβ2 is conserved throughout eukaryotes. Kap104, the Kapβ2 homolog in Saccharomyces cerevisiae, recognizes PY-NLSs in cargos Nab2, Hrp1, and Tfg2. We have determined the crystal structure of Kapβ2 bound to the PY-NLS of the mRNA processing protein Nab2 at 3.05-Å resolution. A seven-residue segment of the PY-NLS of Nab2 is observed to bind Kapβ2 in an extended conformation and occupies the same PY-NLS binding site observed in other Kapβ2•PY-NLS structures. PMID:23535894

Virus-driven Inflammation Is Associated With the Development of bNAbs in Spontaneous Controllers of HIV.

PubMed

Dugast, Anne-Sophie; Arnold, Kelly; Lofano, Giuseppe; Moore, Sarah; Hoffner, Michelle; Simek, Melissa; Poignard, Pascal; Seaman, Michael; Suscovich, Todd J; Pereyra, Florencia; Walker, Bruce D; Lauffenburger, Doug; Kwon, Douglas S; Keele, Brandon F; Alter, Galit

2017-04-15

Understanding the mechanism(s) by which broadly neutralizing antibodies (bNAbs) emerge naturally following infection is crucial for the development of a protective vaccine against human immunodeficiency virus (HIV). Although previous studies have implicated high viremia and associated immune activation as potential drivers for the development of bNAbs, here we sought to unlink the effect of these 2 parameters by evaluating the key inflammatory predictors of bNAb development in HIV-infected individuals who spontaneously control HIV in the absence of antiretroviral therapy ("controllers"). The breadth of antibody-mediated neutralization against 11 tier 2 or 3 viruses was assessed in 163 clade B spontaneous controllers of HIV. Plasma levels of 17 cytokines were screened in the same set of subjects. The relationship of the inflammatory signature was assessed in the context of viral blips or viral RNA levels in peripheral blood or gastrointestinal biopsies from aviremic controllers (<50 copies RNA/mL) and in the context of viral sequence diversity analysis in the plasma of viremic controllers (<50-2000 copies RNA/mL). A unique inflammatory profile, including high plasma levels of CXCL13, sCD40L, IP10, RANTES, and TNFα, was observed in HIV controllers who developed bNAbs. Interestingly, viral load and tissue viremia, but not intermittent viral blips, were associated with these cytokine profiles. However, viral diversity was not significantly associated with increased breadth in controllers. These results suggest that low antigenic diversity in the setting of a unique inflammatory profile associated with antigen persistence may be linked to the evolution of neutralizing antibody breadth. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Intraindividual Variability in Executive Function Performance in Healthy Adults: Cross-Sectional Analysis of the NAB Executive Functions Module.

PubMed

Buczylowska, Dorota; Petermann, Franz

2018-01-01

The current study was aimed at investigating across-tasks intraindividual variability, also termed dispersion, in EF performance. The German adaptation of the Neuropsychological Assessment Battery (NAB) was used as a measure of EFs. Data of 444 participants aged 18-99 from six NAB Executive Functions Module subtests (i.e., Planning, Mazes, Letter Fluency, Judgment, Categories, and Word Generation) along with the NAB Total Index score as a measure of overall cognitive ability were analyzed. Maximum discrepancy (MD) was applied as a measure of dispersion. MD values ranged from 0.47 to 5.20 indicating substantial across-tasks dispersion in EF performance. Furthermore, dispersion moderately decreased with advancing age. Taking overall cognitive ability into account revealed that dispersion might be lower at older ages; especially, when associated with low overall ability levels. The dedifferentiation hypothesis offers a plausible explanation for these findings. That is, the cognitive profiles of older people might be less heterogenous than that of younger people, which may be due to age-related central nervous system constraints.

Intraindividual Variability in Executive Function Performance in Healthy Adults: Cross-Sectional Analysis of the NAB Executive Functions Module

PubMed Central

Buczylowska, Dorota; Petermann, Franz

2018-01-01

The current study was aimed at investigating across-tasks intraindividual variability, also termed dispersion, in EF performance. The German adaptation of the Neuropsychological Assessment Battery (NAB) was used as a measure of EFs. Data of 444 participants aged 18–99 from six NAB Executive Functions Module subtests (i.e., Planning, Mazes, Letter Fluency, Judgment, Categories, and Word Generation) along with the NAB Total Index score as a measure of overall cognitive ability were analyzed. Maximum discrepancy (MD) was applied as a measure of dispersion. MD values ranged from 0.47 to 5.20 indicating substantial across-tasks dispersion in EF performance. Furthermore, dispersion moderately decreased with advancing age. Taking overall cognitive ability into account revealed that dispersion might be lower at older ages; especially, when associated with low overall ability levels. The dedifferentiation hypothesis offers a plausible explanation for these findings. That is, the cognitive profiles of older people might be less heterogenous than that of younger people, which may be due to age-related central nervous system constraints. PMID:29593624

An XMM-Newton Study of the Bright Ultrasoft Narrow-Line Quasar NAB 0205+024

NASA Technical Reports Server (NTRS)

Brandt, Niel

2004-01-01

The broad-band X-ray continuum of NAB 0205424 is well constrained due to the excellent photon statistics obtained (about 97,700 counts), and its impressive soft X-ray excess is clearly apparent. The hard X-ray power law has become notably steeper than when NAB 0205424 was observed with ASCA, attesting to the presence of significant X-ray spectral variability. A strong and broad emission feature is detected from about 5 to 6.4 keV, and we have modeled this as a relativistic line emitted close to the black hole from a narrow annulus of the accretion disk. Furthermore, a strong X-ray flare is detected with a hard X-ray spectrum; this flare may be responsible for illuminating the inner line-emitting part of the accretion disk. The combined observational results can be broadly interpreted in terms of the "thundercloud model proposed by Merloni & Fabian (2001).

Modulating NMDA Receptor Function with D-Amino Acid Oxidase Inhibitors: Understanding Functional Activity in PCP-Treated Mouse Model

PubMed Central

Sershen, Henry; Hashim, Audrey; Dunlop, David S.; Suckow, Raymond F.; Cooper, Tom B.; Javitt, Daniel C.

2016-01-01

Deficits in N-methyl-D-aspartate receptor (NMDAR) function are increasingly linked to persistent negative symptoms and cognitive deficits in schizophrenia. Accordingly, clinical studies have been targeting the modulatory site of the NMDA receptor, based on the decreased function of NMDA receptor, to see whether increasing NMDA function can potentially help treat the negative and cognitive deficits seen in the disease. Glycine and D-serine are endogenous ligands to the NMDA modulatory site, but since high doses are needed to affect brain levels, related compounds are being developed, for example glycine transport (GlyT) inhibitors to potentially elevate brain glycine or targeting enzymes, such as D-amino acid oxidase (DAAO) to slow the breakdown and increase the brain level of D-serine. In the present study we further evaluated the effect of DAAO inhibitors 5-chloro-benzo[d]isoxazol-3-ol (CBIO) and sodium benzoate (NaB) in a phencyclidine (PCP) rodent mouse model to see if the inhibitors affect PCP-induced locomotor activity, alter brain D-serine level, and thereby potentially enhance D-serine responses. D-Serine dose-dependently reduced the PCP-induced locomotor activity at doses above 1000 mg/kg. Acute CBIO (30 mg/kg) did not affect PCP-induced locomotor activity, but appeared to reduce locomotor activity when given with D-serine (600 mg/kg); a dose that by itself did not have an effect. However, the effect was also present when the vehicle (Trappsol®) was tested with D-serine, suggesting that the reduction in locomotor activity was not related to DAAO inhibition, but possibly reflected enhanced bioavailability of D-serine across the blood brain barrier related to the vehicle. With this acute dose of CBIO, D-serine level in brain and plasma were not increased. Another weaker DAAO inhibitor sodium benzoate (NaB) (400 mg/kg), and NaB plus D-serine also significantly reduced PCP-induced locomotor activity, but without affecting plasma or brain D-serine level

Suppression of NGB and NAB/ERabp1 in tomato modifies root responses to potato cyst nematode infestation.

PubMed

Dąbrowska-Bronk, Joanna; Czarny, Magdalena; Wiśniewska, Anita; Fudali, Sylwia; Baranowski, Łukasz; Sobczak, Mirosław; Święcicka, Magdalena; Matuszkiewicz, Mateusz; Brzyżek, Grzegorz; Wroblewski, Tadeusz; Dobosz, Renata; Bartoszewski, Grzegorz; Filipecki, Marcin

2015-05-01

Plant-parasitic nematodes cause significant damage to major crops throughout the world. The small number of genes conferring natural plant resistance and the limitations of chemical control require the development of new protective strategies. RNA interference or the inducible over-expression of nematicidal genes provides an environment-friendly approach to this problem. Candidate genes include NGB, which encodes a small GTP-binding protein, and NAB/ERabp1, which encodes an auxin-binding protein, which were identified as being up-regulated in tomato roots in a transcriptome screen of potato cyst nematode (Globodera rostochiensis) feeding sites. Real-time reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization confirmed the localized up-regulation of these genes in syncytia and surrounding cells following nematode infection. Gene-silencing constructs were introduced into tomato, resulting in a 20%-98% decrease in transcription levels. Nematode infection tests conducted on transgenic plants showed 57%-82% reduction in the number of G. rostochiensis females in vitro and 30%-46% reduction in pot trials. Transmission electron microscopy revealed a deterioration of cytoplasm, and degraded mitochondria and plastids, in syncytia induced in plants with reduced NAB/ERabp1 expression. Cytoplasm in syncytia induced in plants with low NGB expression was strongly electron translucent and contained very few ribosomes; however, mitochondria and plastids remained intact. Functional impairments in syncytial cytoplasm of silenced plants may result from NGB's role in ribosome biogenesis; this was confirmed by localization of yellow fluorescent protein (YFP)-labelled NGB protein in nucleoli and co-repression of NGB in plants with reduced NAB/ERabp1 expression. These results demonstrate that NGB and NAB/ERabp1 play important roles in the development of nematode-induced syncytia. © 2014 BSPP AND JOHN WILEY & SONS LTD.

Nuclear relocation of STAT6 reliably predicts NAB2-STAT6 fusion for the diagnosis of solitary fibrous tumour.

PubMed

Koelsche, Christian; Schweizer, Leonille; Renner, Marcus; Warth, Arne; Jones, David T W; Sahm, Felix; Reuss, David E; Capper, David; Knösel, Thomas; Schulz, Birte; Petersen, Iver; Ulrich, Alexis; Renker, Eva Kristin; Lehner, Burkhard; Pfister, Stefan M; Schirmacher, Peter; von Deimling, Andreas; Mechtersheimer, Gunhild

2014-11-01

Nuclear relocation of STAT6 has been shown in tumours with NAB2-STAT6 fusion, and has been proposed as an ancillary marker for the diagnosis of solitary fibrous tumours (SFTs). The aim of this study was to verify the utility of STAT6 immunohistology in diagnosing SFT. A total of 689 formalin-fixed paraffin-embedded tumours comprising 35 pleural SFTs and 654 other mesenchymal tumours were investigated for STAT6 expression using immunohistochemistry. Nine dedifferentiated liposarcomas (DDLSs) and five SFTs were also examined for the presence of NAB2-STAT6 fusion at the protein level using the proximity ligation assay (PLA), and for copy number variants (CNVs) with the Illumina Infinium Human Methylation450 array. Thirty-four of 35 SFTs showed strong nuclear STAT6 expression. Furthermore, five of 68 DDLSs, two of 130 undifferentiated pleomorphic sarcomas and one of 63 cases of nodular fasciitis showed moderate to strong nuclear STAT6 expression. The PLA indicated the presence of NAB2-STAT6 fusion protein in SFTs, but signal was also detected in some DDLSs. Copy number analysis showed an overall low frequency of chromosomal imbalances in SFTs, but complex karyotypes in DDLSs, including amplification of STAT6 and MDM2 loci. The detection of nuclear relocation of STAT6 with immunohistochemistry is a characteristic of SFTs, and may serve as a diagnostic marker that indicates NAB2-STAT6 fusion and helps to discriminate SFTs from histological mimics. © 2014 John Wiley & Sons Ltd.

A randomized phase II study of weekly nab-paclitaxel plus gemcitabine or simplified LV5FU2 as first-line therapy in patients with metastatic pancreatic cancer: the AFUGEM GERCOR trial.

PubMed

Bachet, Jean-Baptiste; Chibaudel, Benoist; Bonnetain, Franck; Validire, Pierre; Hammel, Pascal; André, Thierry; Louvet, Christophe

2015-10-06

Metastatic pancreatic adenocarcinoma (PAC) prognosis remains dismal and gemcitabine monotherapy has been the standard treatment over the last decade. Currently, two first-line regimens are used in this setting: FOLFIRINOX and nab-paclitaxel plus gemcitabine. Increasing translational data on the predictive value of hENT1 for determining gemcitabine efficacy suggest that a non-gemcitabine-based regimen is favored in about 60 % of patients with PAC due to high resistance of PAC to this cytotoxic drug. This study aims to evaluate the efficacy of weekly nab-paclitaxel combined with gemcitabine or a simplified (s) LV5FU2 regimen in patients with previously untreated metastatic PAC. AFUGEM is a two-stage, open-label, randomized, multicenter, phase II trial. Patients with PAC who meet the inclusion criteria and provide written informed consent will be randomized in a 1:2 ratio to either nab-paclitaxel (125 mg/m(2)) plus gemcitabine (1000 mg/m(2)) given on days 1, 8, and 15 every 28 days or nab-paclitaxel (125 mg/m(2)) plus sLV5FU2 (leucovorin 400 mg/m(2) followed by bolus 400 mg/m(2) 5-fluorouracil and by 5-fluorouracil 2400 mg/m(2) as an 46-h intravenous infusion) given on days 1 and 15 every 28 days. A total of 114 patients will be randomized to one of the treatment arms. The primary endpoint is progression-free survival at 4 months. Secondary outcomes are rate and duration of response, disease control, overall survival, safety, and quality of life. Potential biomarkers of gemcitabine (hENT1, dCK) and 5-fluorouracil (TS) efficacy will be assessed. The AFUGEM trial is designed to provide valuable information regarding efficacy and tolerability of nab-paclitaxel plus gemcitabine and nab-paclitaxel plus sLV5FU2 regimens. Identification of potential predictive biomarkers of gemcitabine and 5-fluorouracil is likely to drive therapeutic decisions in patients with metastatic PAC. AFUGEM is registered at Clinicaltrials.gov: NCT01964534 , October 15, 2013.

75 FR 38129 - TRW Automotive, Kelsey-Hayes Company, NABS Division, Mt. Vernon, OH; Amended Certification...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-01

... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-70,907] TRW Automotive, Kelsey... Adjustment Assistance on August 25, 2009, applicable to workers of TRW Automotive, NABS Division, Mt. Vernon... for the automotive industry. Information shows that some workers separated from employment at the...

Detection system for neutron β decay correlations in the UCNB and Nab experiments

DOE PAGES

Broussard, L. J.; Oak Ridge National Lab.; Zeck, B. A.; ...

2016-12-19

Here, we describe a detection system designed to precisely measure multiple correlations in neutron β decay. Furthermore, the system is based on thick, large area, highly segmented silicon detectors developed in collaboration with Micron Semiconductor, Ltd. The prototype system meets specifications of energy thresholds below 10 keV, energy resolution of ~3 keV FWHM, and rise time of ~50 ns with 19 of the 127 detector pixels instrumented. We have demonstrated the coincident detection of β particles and recoil protons from neutron β decay, using ultracold neutrons at the Los Alamos Neutron Science Center, . The fully instrumented detection system willmore » be implemented in the UCNB and Nab experiments, to determine the neutron β decay parameters B, a, and b.« less

Treatment Rationale and Design for J-SONIC: A Randomized Study of Carboplatin Plus Nab-paclitaxel With or Without Nintedanib for Advanced Non-Small-cell Lung Cancer With Idiopathic Pulmonary Fibrosis.

PubMed

Otsubo, Kohei; Kishimoto, Junji; Kenmotsu, Hirotsugu; Minegishi, Yuji; Ichihara, Eiki; Shiraki, Akira; Kato, Terufumi; Atagi, Shinji; Horinouchi, Hidehito; Ando, Masahiko; Kondoh, Yasuhiro; Kusumoto, Masahiko; Ichikado, Kazuya; Yamamoto, Nobuyuki; Nakanishi, Yoichi; Okamoto, Isamu

2018-01-01

We describe the treatment rationale and procedure for a randomized study (J-SONIC; University Hospital Medical Information Network Clinical Trials Registry identification no., UMIN000026799) of carboplatin plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel) with or without nintedanib for patients with advanced non-small cell lung cancer (NSCLC) and idiopathic pulmonary fibrosis (IPF). The study was designed to examine the efficacy and safety of nintedanib administered with carboplatin plus nab-paclitaxel versus carboplatin plus nab-paclitaxel alone in chemotherapy-naive patients with advanced NSCLC associated with IPF. Eligible patients (enrollment target, n = 170) will be randomized at a 1:1 ratio to receive 4 cycles of carboplatin (area under the curve, 6 on day 1) plus nab-paclitaxel (100 mg/m 2 on days 1, 8, and 15) administered every 3 weeks either without (arm A) or with (arm B) nintedanib (150 mg twice daily), to be followed in arm B by single-agent administration of nintedanib (150 mg twice daily). The present trial is the first randomized controlled study for the treatment of NSCLC associated with IPF. The goal of the study is to demonstrate that nintedanib combined with carboplatin plus nab-paclitaxel prolongs the interval to acute exacerbation of IPF compared with carboplatin plus nab-paclitaxel alone. Copyright © 2017 Elsevier Inc. All rights reserved.

Development and characterization of a pre-treatment procedure to eliminate human monoclonal antibody therapeutic drug and matrix interference in cell-based functional neutralizing antibody assays.

PubMed

Xu, Weifeng; Jiang, Hao; Titsch, Craig; Haulenbeek, Jonathan R; Pillutla, Renuka C; Aubry, Anne-Françoise; DeSilva, Binodh S; Arnold, Mark E; Zeng, Jianing; Dodge, Robert W

2015-01-01

Biological therapeutics can induce an undesirable immune response resulting in the formation of anti-drug antibodies (ADA), including neutralizing antibodies (NAbs). Functional (usually cell-based) NAb assays are preferred to determine NAb presence in patient serum, but are often subject to interferences from numerous serum factors, such as growth factors and disease-related cytokines. Many functional cell-based NAb assays are essentially drug concentration assays that imply the presence of NAbs by the detection of small changes in functional drug concentration. Any drug contained in the test sample will increase the total amount of drug in the assay, thus reducing the sensitivity of NAb detection. Biotin-drug Extraction with Acid Dissociation (BEAD) has been successfully applied to extract ADA, thereby removing drug and other interfering factors from human serum samples. However, to date there has been no report to estimate the residual drug level after BEAD treatment when the drug itself is a human monoclonal antibody; mainly due to the limitation of traditional ligand-binding assays. Here we describe a universal BEAD optimization procedure for human monoclonal antibody (mAb) drugs by using a LC-MS/MS method to simultaneously measure drug (a mutant human IgG4), NAb positive control (a mouse IgG), and endogenous human IgGs as an indicator of nonspecific carry-over in the BEAD eluate. This is the first report demonstrating that residual human mAb drug level in clinical sample can be measured after BEAD pre-treatment, which is critical for further BEAD procedure optimization and downstream immunogenicity testing. Copyright © 2014 Elsevier B.V. All rights reserved.

Efficacy and safety of nab-paclitaxel in patients with previously treated metastatic colorectal cancer: a phase II COLO-001 trial.

PubMed

Ducreux, Michel; Bennouna, Jaafar; Adenis, Antoine; Conroy, Thierry; Lièvre, Astrid; Portales, Fabienne; Jeanes, Julie; Li, Li; Romano, Alfredo

2017-01-01

This single-arm, phase II trial evaluated nab-paclitaxel monotherapy in pretreated patients with metastatic colorectal cancer (mCRC). Patients with mCRC (RAS wild-type and RAS mutant cohorts) received nab-paclitaxel 125 mg/m 2 days 1, 8, and 15 (28-day cycle). The primary endpoint was investigator-assessed progression-free survival (PFS) rate at week 8; secondary endpoints included overall survival, overall response rate, and safety. Stage 1 planned enrollment was 15 patients per cohort per Simon 2-stage design. Stage 2 enrollment was to continue unless ≤8 of the first 15 patients per cohort achieved PFS at 8 weeks. Stage 1 enrolled 41 patients (RAS wild type: n = 18; RAS mutant: n = 23). In both RAS cohorts, 3 of 15 patients initially enrolled were progression-free at week 8 (20%; 95% CI 4.0-48.0). Median PFS was 8.1 weeks (95% CI 7.7-8.6) and 7.9 weeks (95% CI 7.6-8.0) for RAS wild-type and RAS mutant cohorts, respectively. There were no complete or partial responses. The overall disease control rate was 16% (95% CI 6.0-32.0), and rates were similar in the RAS wild-type and RAS mutant cohorts (18 and 15%, respectively). No new safety signals were reported; the most common grade ≥3 adverse events included neutropenia, asthenia, and peripheral neuropathy. This study did not progress to stage 2 per the preplanned statistical stopping rule. In patients with heavily pretreated mCRC, nab-paclitaxel did not demonstrate promising antitumor activity; further assessment of nab-paclitaxel monotherapy in this population of patients is not supported. NCT02103062.

Aspirin-triggered lipoxin A4 and lipoxin A4 up-regulate transcriptional corepressor NAB1 in human neutrophils.

PubMed

Qiu, F H; Devchand, P R; Wada, K; Serhan, C N

2001-12-01

Aspirin-triggered 15-epi-lipoxin A4 (ATL) is an endogenous lipid mediator that mimics the actions of native lipoxin A4, a putative "stop signal" involved in regulating resolution of inflammation. A metabolically more stable analog of ATL, 15-epi-16-(para-fluoro)-phenoxy-lipoxin A4 analog (ATLa), inhibits neutrophil recruitment in vitro and in vivo and displays potent anti-inflammatory actions. ATLa binds with high affinity to the lipoxin A4 receptor, a G protein-coupled receptor on the surface of leukocytes. In this study, we used freshly isolated human neutrophils to examine ATLa's potential for initiating rapid nuclear responses. Using differential display reverse transcription polymerase chain reaction, we identified a subset of genes that was selectively up-regulated upon short exposure of polymorphonuclear leukocytes to ATLa but not to the chemoattractant leukotriene B4 or vehicle alone. We further investigated ATLa regulation of one of the genes, NAB1, a transcriptional corepressor identified previously as a glucocorticoid-responsive gene in hamster smooth muscle cells. Treatment of human neutrophils with pertussis toxin blocked ATLa up-regulation of NAB1. In addition, ATLa stimulated NAB1 gene expression in murine lung vascular smooth muscle in vivo. These findings provide evidence for rapid transcriptional induction of a cassette of genes via an ATLa-stimulated G protein-coupled receptor pathway that is potentially protective and overlaps with the anti-inflammatory glucocorticoid regulatory circuit.

nab-paclitaxel potentiates gemcitabine activity by reducing cytidine deaminase levels in a mouse model of pancreatic cancer

PubMed Central

Cook, Natalie; Bapiro, Tashinga E.; Lolkema, Martijn P.; Jodrell, Duncan I.; Tuveson, David A.

2016-01-01

nab-paclitaxel, an albumin-stabilized paclitaxel formulation, demonstrates clinical activity when administered in combination with gemcitabine in patients with metastatic pancreatic ductal adenocarcinoma (PDA). The limited availability of patient tissue and exquisite sensitivity of xenografts to chemotherapeutics have limited our ability to address the mechanistic basis of this treatment regimen. Here, we used a mouse model of PDA to show that the co-administration of nab-paclitaxel and gemcitabine uniquely demonstrates evidence of tumor regression. Combination treatment increases intratumoral gemcitabine levels due to a marked decrease in the primary gemcitabine metabolizing enzyme, cytidine deaminase (Cda). Correspondingly, paclitaxel reduced Cda protein levels in cultured cells through reactive oxygen species-mediated degradation, resulting in the increased stabilization of gemcitabine. Our findings support the concept that suboptimal intratumoral concentrations of gemcitabine represent a crucial mechanism of therapeutic resistance in PDA and highlight the advantages of genetically engineered mouse models in preclinical therapeutic trials. PMID:22585996

Canine distemper virus neutralization activity is low in human serum and it is sensitive to an amino acid substitution in the hemagglutinin protein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Xinsheng, E-mail: xzhang@iavi.org; Molecular and Cellular Biology Program, State University of New York, Brooklyn, NY; Wallace, Olivia L.

Serum was analyzed from 146 healthy adult volunteers in eastern Africa to evaluate measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb) prevalence and potency. MV plaque reduction neutralization test (PRNT) results indicated that all sera were positive for MV nAbs. Furthermore, the 50% neutralizing dose (ND50) for the majority of sera corresponded to antibody titers induced by MV vaccination. CDV nAbs titers were low and generally were detected in sera with high MV nAb titers. A mutant CDV was generated that was less sensitive to neutralization by human serum. The mutant virus genome had 10 nucleotide substitutions,more » which coded for single amino acid substitutions in the fusion (F) and hemagglutinin (H) glycoproteins and two substitutions in the large polymerase (L) protein. The H substitution occurred in a conserved region involved in receptor interactions among morbilliviruses, implying that this region is a target for cross-reactive neutralizing antibodies. - Highlights: • Screened 146 serum samples for measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb). • MV nAb is prevalent in the sera. • CDV neutralizing activity is generally low or absent and when detected it is present in sera with high MV nAb titers. • A neutralization-resistant CDV mutant was isolated using human serum selection. • A mutation was identified in the receptor-binding region of CDV hemagglutinin protein that confers the neutralization resistance.« less

Identification of NAB1, a repressor of NGFI-A- and Krox20-mediated transcription.

PubMed Central

Russo, M W; Sevetson, B R; Milbrandt, J

1995-01-01

NGFI-A (also called Egr1, Zif268, or Krox24) and the closely related proteins Krox20, NGFI-C, and Egr3 are zinc-finger transcription factors encoded by immediate-early genes which are induced by a wide variety of extracellular stimuli. NGFI-A has been implicated in cell proliferation, macrophage differentiation, synaptic activation, and long-term potentiation, whereas Krox20 is critical for proper hindbrain segmentation and peripheral nerve myelination. In previous work, a structure/function analysis of NGFI-A revealed a 34-aa inhibitory domain that was hypothesized to be the target of a cellular factor that represses NGFI-A transcriptional activity. Using the yeast two-hybrid system, we have isolated a cDNA clone which encodes a protein that interacts with this inhibitory domain and inhibits the ability of NGFI-A to activate transcription. This NGFI-A-binding protein, NAB1, is a 570-aa nuclear protein that bears no obvious sequence homology to known proteins. NAB1 also represses Krox20 activity, but it does not influence Egr3 or NGFI-G, thus providing a mechanism for the differential regulation of this family of immediate-early transcription factors. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:7624335

Adventitial nab-rapamycin injection reduces porcine femoral artery luminal stenosis induced by balloon angioplasty via inhibition of medial proliferation and adventitial inflammation.

PubMed

Gasper, Warren J; Jimenez, Cynthia A; Walker, Joy; Conte, Michael S; Seward, Kirk; Owens, Christopher D

2013-12-01

Endovascular interventions on peripheral arteries are limited by high rates of restenosis. Our hypothesis was that adventitial injection of rapamycin nanoparticles would be safe and reduce luminal stenosis in a porcine femoral artery balloon angioplasty model. Eighteen juvenile male crossbred swine were included. Single-injury (40%-60% femoral artery balloon overstretch injury; n=2) and double-injury models (endothelial denudation injury 2 weeks before a 20%-30% overstretch injury; n=2) were compared. The double-injury model produced significantly more luminal stenosis at 28 days, P=0.002, and no difference in medial fibrosis or inflammation. Four pigs were randomized to the double-injury model and adventitial injection of saline (n=2) or 500 μg of nanoparticle albumin-bound rapamycin (nab-rapamycin; n=2) with an endovascular microinfusion catheter. There was 100% procedural success and no difference in endothelial regeneration. At 28 days, nab-rapamycin led to significant reductions in luminal stenosis, 17% (interquartile range, 12%-35%) versus 10% (interquartile range, 8.3%-14%), P=0.001, medial cell proliferation, P<0.001, and fibrosis, P<0.001. There were significantly fewer adventitial leukocytes at 3 days, P<0.001, but no difference at 28 days. Pharmacokinetic analysis (single-injury model) found rapamycin concentrations 1500× higher in perivascular tissues than in blood at 1 hour. Perivascular rapamycin persisted ≥8 days and was not detectable at 28 days. Adventitial nab-rapamycin injection was safe and significantly reduced luminal stenosis in a porcine femoral artery balloon angioplasty model. Observed reductions in early adventitial leukocyte infiltration and late medial cell proliferation and fibrosis suggest an immunosuppressive and antiproliferative mechanism. An intraluminal microinfusion catheter for adventitial injection represents an alternative to stent- or balloon-based local drug delivery.

'Papillary' solitary fibrous tumor/hemangiopericytoma with nuclear STAT6 expression and NAB2-STAT6 fusion.

PubMed

Ishizawa, Keisuke; Tsukamoto, Yoshitane; Ikeda, Shunsuke; Suzuki, Tomonari; Homma, Taku; Mishima, Kazuhiko; Nishikawa, Ryo; Sasaki, Atsushi

2016-04-01

This report describes clinicopathological findings, including genetic data of STAT6, in a solitary fibrous tumor (SFT)/hemangiopericytoma (HPC) of the central nervous system in an 83-year-old woman with a bulge in the left forehead. She noticed it about 5 months before, and it had grown rapidly for the past 1 month. Neuroradiological studies disclosed a well-demarcated tumor that accompanied the destruction of the skull. The excised tumor showed a prominent papillary structure, where atypical cells were compactly arranged along the fibrovascular core ('pseudopapillary'). There was rich vasculature, some of which resembled 'staghorn' vessels. Mitotic figures were occasionally found. Whorls, psammoma bodies, or intra-nuclear pseudoinclusions were not identified. By immunohistochemistry, CD34 was strongly positive in the tumor cells, and STAT6 was localized in their nuclei. By reverse transcription-polymerase chain reaction (RT-PCR), an NAB2-STAT6 fusion gene, NAB2 exon6-STAT6 exon17, was detected, establishing a definite diagnosis of SFT/HPC. 'Papillary' SFT/HPC needs to be recognized as a possible morphological variant of SFT/HPC, and should be borne in mind in its diagnostic practice.

A phase II study of nab-paclitaxel plus carboplatin in combination with thoracic radiation in patients with locally advanced non–small-cell lung cancer

PubMed Central

Hasegawa, Takaaki; Futamura, Yohei; Horiba, Akane; Yoshida, Tsutomu; Suzuki, Toshitaka; Kato, Tatsuo; Kaito, Daizo; Ohno, Yasuhi; Iida, Takayoshi; Hayashi, Shinya; Sawa, Toshiyuki

2016-01-01

We investigated the efficacy and safety of albumin-bound paclitaxel (nab-PTX) and carboplatin (CBDCA) with concurrent radiotherapy for unresectable locally advanced non–small-cell lung cancer (NSCLC). Patients with Stage III NSCLC and an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible. Concurrent chemoradiotherapy consisted of weekly administration of nab-PTX (40 mg/m2) plus CBDCA (area under the plasma concentration time curve (AUC) 2) and thoracic radiotherapy (60 Gy/30 fractions) for a total of 6 weeks. After concurrent chemoradiotherapy, patients received an additional two cycles of consolidation phase chemotherapy that consisted of 4-week cycles of nab-PTX (100 mg/m2 on Days 1, 8 and 15)/CBDCA (AUC 5 mg/ml/min on Day 1). Response was evaluated in accordance with the Response Evaluation Criteria in Solid Tumors. Progression-free survival and overall survival were estimated using the Kaplan–Meier method. Toxicity was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events. A total of 10 patients were enrolled in this trial between September 2013 and January 2014 from three institutes. The overall response rate was 40.0% and the median progression-free survival was 6.7 months. Treatment-related death occurred in two patients. Grade 2 or worse severe radiation pneumonitis was observed in all three patients that had the volume of lung receiving at least 20 Gy (V20) >30%. The results of this study indicate that no further investigation is warranted into nab-PTX and CBDCA with concurrent thoracic radiation for Stage III NSCLC with V20 > 30% due to severe toxicity. PMID:26442970

Novel view on the mechanism of water-assisted proton transfer in the DNA bases: bulk water hydration.

PubMed

Furmanchuk, Al'ona; Isayev, Olexandr; Gorb, Leonid; Shishkin, Oleg V; Hovorun, Dmytro M; Leszczynski, Jerzy

2011-03-14

In the present work, the conventional static ab initio picture of a water-assisted mechanism of the tautomerization of Nucleic Acid Bases (NABs) in an aqueous environment is enhanced by the classical and Car-Parrinello molecular dynamics simulations. The inclusion of the dynamical contribution is vital because the formation and longevity of the NAB-water bridge complexes represent decisive factors for further tautomerization. The results of both molecular dynamic techniques indicate that the longest time when such complexes exist is significantly shorter than the time required for proton transfer suggested by the static ab initio level of theory. New rate constants of tautomerization corrected for the dynamic effect of environment are proposed based on the first principles molecular dynamics data. Those values are used for the evaluation of a water-assisted mechanism that is feasible in such biological systems as E. coli cell.

A phase II study of nab-paclitaxel plus carboplatin in combination with thoracic radiation in patients with locally advanced non-small-cell lung cancer.

PubMed

Hasegawa, Takaaki; Futamura, Yohei; Horiba, Akane; Yoshida, Tsutomu; Suzuki, Toshitaka; Kato, Tatsuo; Kaito, Daizo; Ohno, Yasuhi; Iida, Takayoshi; Hayashi, Shinya; Sawa, Toshiyuki

2016-01-01

We investigated the efficacy and safety of albumin-bound paclitaxel (nab-PTX) and carboplatin (CBDCA) with concurrent radiotherapy for unresectable locally advanced non-small-cell lung cancer (NSCLC). Patients with Stage III NSCLC and an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible. Concurrent chemoradiotherapy consisted of weekly administration of nab-PTX (40 mg/m(2)) plus CBDCA (area under the plasma concentration time curve (AUC) 2) and thoracic radiotherapy (60 Gy/30 fractions) for a total of 6 weeks. After concurrent chemoradiotherapy, patients received an additional two cycles of consolidation phase chemotherapy that consisted of 4-week cycles of nab-PTX (100 mg/m(2) on Days 1, 8 and 15)/CBDCA (AUC 5 mg/ml/min on Day 1). Response was evaluated in accordance with the Response Evaluation Criteria in Solid Tumors. Progression-free survival and overall survival were estimated using the Kaplan-Meier method. Toxicity was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events. A total of 10 patients were enrolled in this trial between September 2013 and January 2014 from three institutes. The overall response rate was 40.0% and the median progression-free survival was 6.7 months. Treatment-related death occurred in two patients. Grade 2 or worse severe radiation pneumonitis was observed in all three patients that had the volume of lung receiving at least 20 Gy (V20) >30%. The results of this study indicate that no further investigation is warranted into nab-PTX and CBDCA with concurrent thoracic radiation for Stage III NSCLC with V20 > 30% due to severe toxicity. © The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Stereological studies of the effects of sodium benzoate or ascorbic acid on rats` cerebellum.

PubMed

Noorafshan, Ali; Erfanizadeh, Mahboobeh; Karbalay-Doust, Saied

2014-12-01

To evaluate the cerebellar structure in sodium benzoate (NaB) or ascorbic acid (AA) treated rats. This experimental study was conducted between May and September 2013 in the Laboratory Animal Center of Shiraz University of Medical Sciences, Shiraz, Iran. The rats received distilled either water, NaB (200mg/kg/day), AA (100mg/kg/day), or NaB+AA. The hemispheres were removed after 28 days and underwent quantitative study. The total volume of the cerebellar hemisphere, its cortex, intracerebellar nuclei; the total number of the Purkinje, Bergman, granule, neurons, and glial cells of the molecular layer; and neurons and glial cells of the intracerebellar nuclei reduced by 21-52% in the NaB-treated rats compared with the distilled water group (p=0.004). The total number of the Purkinje, Bergman, Golgi, and granule cells was 29-45% higher in the AA-treated rats compared with the distilled water group (p=0.05). However, these measures reduced by 17-50% in the NaB+AA-treated rats compared with the distilled water group (p=0.004). The NaB+AA group did not induce any significant structural changes in comparison with the NaB group (p>0.05). The NaB exposure with or without AA treatment could alter the cerebellum. Yet, AA could prevent the loss of some cells in the cerebellum. 

Age-related commonalities and differences in the relationship between executive functions and intelligence: Analysis of the NAB executive functions module and WAIS-IV scores.

PubMed

Buczylowska, Dorota; Petermann, Franz

2017-01-01

Data from five subtests of the Executive Functions Module of the German Neuropsychological Assessment Battery (NAB) and all ten core subtests of the German Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV) were used to examine the relationship between executive functions and intelligence in a comparison of two age groups: individuals aged 18-59 years and individuals aged 60-88 years. The NAB subtests Categories and Word Generation demonstrated a consistent correlation pattern for both age groups. However, the NAB Judgment subtest correlated more strongly with three WAIS-IV indices, the Full Scale IQ (FSIQ), and the General Ability Index (GAI) in the older adult group than in the younger group. Additionally, in the 60-88 age group, the Executive Functions Index (EFI) was more strongly correlated with the Verbal Comprehension Index (VCI) than with the Perceptual Reasoning Index (PRI). Both age groups demonstrated a strong association of the EFI with the FSIQ and the Working Memory Index (WMI). The results imply the potential diagnostic utility of the Judgment subtest and a significant relationship between executive functioning and crystallized intelligence at older ages. Furthermore, it may be concluded that there is a considerable age-independent overlap between the EFI and general intelligence, as well as between the EFI and working memory.

Phase I results of a phase I/II study of weekly nab-paclitaxel in paediatric patients with recurrent/refractory solid tumours: A collaboration with innovative therapies for children with cancer.

PubMed

Moreno, Lucas; Casanova, Michela; Chisholm, Julia C; Berlanga, Pablo; Chastagner, Pascal B; Baruchel, Sylvain; Amoroso, Loredana; Melcón, Soledad Gallego; Gerber, Nicolas U; Bisogno, Gianni; Fagioli, Franca; Geoerger, Birgit; Glade Bender, Julia L; Aerts, Isabelle; Bergeron, Christophe; Hingorani, Pooja; Elias, Ileana; Simcock, Mathew; Ferrara, Stefano; Le Bruchec, Yvan; Slepetis, Ruta; Chen, Nianhang; Vassal, Gilles

2018-06-21

nab-Paclitaxel has demonstrated efficacy in adults with solid tumours and preclinical activity in paediatric solid tumour models. Results from phase I of a phase I/II study in paediatric patients with recurrent/refractory solid tumours treated with nab-paclitaxel are reported. Patients with recurrent/refractory extracranial solid tumours received nab-paclitaxel on days 1, 8 and 15 every 4 weeks at 120, 150, 180, 210, 240, or 270 mg/m 2 (rolling-6 dose-escalation) to establish the maximum tolerated dose (MTD) and recommended phase II dose (RP2D). Sixty-four patients were treated. Dose-limiting toxicities were grade 3 dizziness at 120 mg/m 2 and grade 4 neutropenia >7 days at 270 mg/m 2 . The most frequent grade 3/4 adverse events were haematologic, including neutropenia (36%), leukopenia (36%) and lymphopenia (25%). Although the MTD was not reached, 270 mg/m 2 was declared non-tolerable due to grade 3/4 toxicities during cycles 1-2 (neutropenia, n = 5/7; skin toxicity, n = 2/7; peripheral neuropathy, n = 1/7). Of 58 efficacy-evaluable patients, complete response occurred in one patient (2%; Ewing sarcoma) and partial responses in four patients (7%; rhabdomyosarcoma, Ewing sarcoma, renal tumour with pulmonary metastases [high-grade, malignant] and sarcoma not otherwise specified); all responses occurred at ≥210 mg/m 2 . Thirteen patients (22%) had stable disease (5 lasting ≥16 weeks) per RECIST. nab-Paclitaxel 240 mg/m 2 qw3/4 (nearly double the adult recommended monotherapy dose for this schedule in metastatic breast cancer) was selected as the RP2D based on the tolerability profile, pharmacokinetics and antitumour activity. Phase II is currently enrolling patients with recurrent/refractory neuroblastoma, rhabdomyosarcoma and Ewing sarcoma. CLINICALTRIALS.GOV: NCT01962103. 2013-000144-26. Copyright © 2018 Elsevier Ltd. All rights reserved.

A blood-based predictor for neocortical Aβ burden in Alzheimer's disease: results from the AIBL study.

PubMed

Burnham, S C; Faux, N G; Wilson, W; Laws, S M; Ames, D; Bedo, J; Bush, A I; Doecke, J D; Ellis, K A; Head, R; Jones, G; Kiiveri, H; Martins, R N; Rembach, A; Rowe, C C; Salvado, O; Macaulay, S L; Masters, C L; Villemagne, V L

2014-04-01

Dementia is a global epidemic with Alzheimer's disease (AD) being the leading cause. Early identification of patients at risk of developing AD is now becoming an international priority. Neocortical Aβ (extracellular β-amyloid) burden (NAB), as assessed by positron emission tomography (PET), represents one such marker for early identification. These scans are expensive and are not widely available, thus, there is a need for cheaper and more widely accessible alternatives. Addressing this need, a blood biomarker-based signature having efficacy for the prediction of NAB and which can be easily adapted for population screening is described. Blood data (176 analytes measured in plasma) and Pittsburgh Compound B (PiB)-PET measurements from 273 participants from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study were utilised. Univariate analysis was conducted to assess the difference of plasma measures between high and low NAB groups, and cross-validated machine-learning models were generated for predicting NAB. These models were applied to 817 non-imaged AIBL subjects and 82 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) for validation. Five analytes showed significant difference between subjects with high compared to low NAB. A machine-learning model (based on nine markers) achieved sensitivity and specificity of 80 and 82%, respectively, for predicting NAB. Validation using the ADNI cohort yielded similar results (sensitivity 79% and specificity 76%). These results show that a panel of blood-based biomarkers is able to accurately predict NAB, supporting the hypothesis for a relationship between a blood-based signature and Aβ accumulation, therefore, providing a platform for developing a population-based screen.

Comparison of effect of an increased dosage of vonoprazan versus vonoprazan plus lafutidine on gastric acid inhibition and serum gastrin.

PubMed

Suzuki, Takahiro; Kagami, Takuma; Uotani, Takahiro; Yamade, Mihoko; Hamaya, Yasushi; Iwaizumi, Moriya; Osawa, Satoshi; Sugimoto, Ken; Miyajima, Hiroaki; Furuta, Takahisa

2018-01-01

Vonoprazan, a novel potassium-competitive acid blocker, elicits potent acid inhibition and hypergastrinemia at a dose of 20 mg. Its recommended maintenance dose for gastro-esophageal reflux disease is 10 mg, which is sometimes insufficient for preventing nocturnal acid breakthrough (NAB). Concomitant use of a histamine 2 receptor antagonist (H 2 RA) is effective for NAB. However, further acid inhibition by addition of H2RA has concern of hypergastrinemia again. Lafutidine (H2RA) is known to stimulate somatostatin release. The aim of this study is to compare the levels of acid inhibition and serum gastrin attained by addition of lafutidine to vonoprazan 10 mg with levels after a dose increase of vonoprazan from 10 to 20 mg. Thirteen healthy volunteers underwent 24-h intragastric pH monitoring and serum gastrin measurements on day 7 of three different regimens: vonoprazan 10 mg, vonoprazan 10 mg plus lafutidine 10 mg, and vonoprazan 20 mg. Median pH 4 holding time ratios (range) by vonoprazan 10 mg, vonoprazan 10 mg plus lafutidine 10 mg, and vonoprazan 20 mg were 82% (47-88%), 88% (76-93%), and 99% (95-100%) while those at nighttime from 10 p.m. to 8 a.m. were 94% (29-100%), 100% (95-100%), and 100%, respectively. The incidences of NAB with vonoprazan 10 mg, vonoprazan plus lafutidine, and vonoprazan 20 mg were 38, 8, and 0%, respectively. Respective serum gastrin levels were 420 (173-508), 323 (196-521), and 504 (400-812) pg/ml. Addition of lafutidine 10 mg to vonoprazan 10 mg achieved sufficient acid inhibition, especially at nighttime, without further increase of serum gastrin levels.

Recommendations for the validation of cell-based assays used for the detection of neutralizing antibody immune responses elicited against biological therapeutics.

PubMed

Gupta, Shalini; Devanarayan, Viswanath; Finco, Deborah; Gunn, George R; Kirshner, Susan; Richards, Susan; Rup, Bonita; Song, An; Subramanyam, Meena

2011-07-15

The administration of biological therapeutics may result in the development of anti-drug antibodies (ADAs) in treated subjects. In some cases, ADA responses may result in the loss of therapeutic efficacy due to the formation of neutralizing ADAs (NAbs). An important characteristic of anti-drug NAbs is their direct inhibitory effect on the pharmacological activity of the therapeutic. Neutralizing antibody responses are of particular concern for biologic products with an endogenous homolog whose activity can be potentially dampened or completely inhibited by the NAbs leading to an autoimmune-type deficiency syndrome. Therefore, it is important that ADAs are detected and characterized appropriately using sensitive and reliable methods. The design, development and optimization of cell-based assays used for detection of NAbs have been published previously by Gupta et al. 2007 [1]. This paper provides recommendations on best practices for the validation of cell-based NAb assay and suggested validation parameters based on the experience of the authors. Copyright © 2011 Elsevier B.V. All rights reserved.

Calibration and Characterization of the UNCB and Nab Detectors

NASA Astrophysics Data System (ADS)

Zeck, Bryan; UCNB Collaboration; Nab Collaboration

2017-09-01

The UCNB and Nab experiments are designed to produce precision measurements of the free neutron decay angular correlations B, a, and b. Measurements of B and a require a coincident detection of the proton and electron produced in neutron decay, while for b, which manifests as a subtle shift in the electron energy spectrum, energy resolution better than 3 keV is desired and excellent fidelity for energy reconstruction is required, including characterization of non-linearity to the 10-4 level. To this end, a thick segmented silicon detector with a 100 nm dead layer and a 100 cm active area has been extensively characterized at LANL. The thin dead layer allows protons accelerated to 30 keV to deposit energy above threshold in the active volume of the detector, and the paired amplifer chain, developed at LANL, has a risetime of approximately 40 ns. Comparison of simulation to experiment reveals a detector resolution better than σ = 2.5 keV. A complete characterization of the detector will be presented. This work has been supported by Grants from the US National Science Foundation and the Department of Energy.

A phase 1/1B trial of ADI-PEG 20 plus nab-paclitaxel and gemcitabine in patients with advanced pancreatic adenocarcinoma.

PubMed

Lowery, Maeve A; Yu, Kenneth H; Kelsen, David Paul; Harding, James J; Bomalaski, John S; Glassman, Danielle C; Covington, Christina M; Brenner, Robin; Hollywood, Ellen; Barba, Adalberto; Johnston, Amanda; Liu, Kay Chia-Wei; Feng, Xiaoxing; Capanu, Marinela; Abou-Alfa, Ghassan K; O'Reilly, Eileen M

2017-12-01

ADI-PEG 20 is a pegylated form of the arginine-depleting enzyme arginine deiminase. Normal cells synthesize arginine with the enzyme argininosuccinate synthetase (ASS1); ADI-PEG 20 selectively targets malignant cells, which lack ASS1. A single-arm, nonrandomized, open-label, phase 1/1B, standard 3 + 3 dose escalation with an expansion cohort of 9 patients at the recommended phase 2 dose (RP2D) was conducted. Patients who had metastatic pancreatic cancer, up to 1 line of prior treatment (the dose-escalation cohort) or no prior treatment (the expansion cohort), and an Eastern Cooperative Oncology Group performance status of 0 to 1 were included. Patients received both gemcitabine (1000 mg/m 2 ) and nab-paclitaxel (125 mg/m 2 ) for 3 of 4 weeks and intramuscular ADI-PEG 20 at 18 mg/m 2 weekly (cohort 1) or at 36 mg/m 2 weekly (cohort 2 and the expansion cohort).The primary endpoint was to determine the maximum tolerated dose and RP2D of ADI-PEG 20 in combination with nab-paclitaxel and gemcitabine. Eighteen patients were enrolled. No dose-limiting toxicities (DLTs) were observed in cohort 1; cohort 2 was expanded to 6 patients because of 1 DLT occurrence (a grade 3 elevation in bilirubin, aspartate aminotransferase, and alanine aminotransferase). The most frequent adverse events (AEs) of any grade were neutropenia, thrombocytopenia, leukopenia, anemia, peripheral neuropathy, and fatigue; all 18 patients experienced grade 3/4 AEs. The most frequent grade 3/4 toxicities, regardless of the relation with any drugs, included neutropenia (12 patients or 67%), leukopenia (10 patients or 56%), anemia (8 patients or 44%), and lymphopenia (6 patients or 33%). The RP2D for ADI-PEG 20 was 36 mg/m 2 weekly in combination with standard-dose gemcitabine and nab-paclitaxel. The overall response rate among patients treated at the RP2D in the first-line setting was 45.5% (5 of 11).The median progression-free survival time for these patients treated at the RP2D was 6.1 months (95

Phase II study of neoadjuvant therapy with nab-paclitaxel and cisplatin followed by surgery in patients with locally advanced esophageal squamous cell carcinoma

PubMed Central

Fan, Yun; Jiang, Youhua; Zhou, Xinming; Chen, Qixun; Huang, Zhiyu; Xu, Yanjun; Gong, Lei; Yu, Haifeng; Yang, Haiyan; Liu, Jinshi; Lei, Tao; Zhao, Qiang; Mao, Weimin

2016-01-01

Background We carried out a phase II study to evaluate the efficiency and safety of the combination of nanoparticle albumin bound-paclitaxel (nab-paclitaxel) and cisplatin as preoperative chemotherapy for locally advanced esophageal squamous cell carcinoma (ESCC) Results From Oct 2011 to Dec 2012, 35 patients were enrolled and received neoadjuvant chemotherapy. Thirty patients underwent surgery and achieved a 100% R0 resection. Pathological complete response (pCR) rate was 13.3% and near pCR rate was 6.7%. Down-staging was achieved in 19 patients. With median follow-up of 37.8 months, 16 patients were still alive. One-, 2- and 3- year overall survival (OS) rate was 90.0%, 70.0% and 43.3%, respectively. This treatment resulted in a median disease-free survival (DFS) of 34.7 months and a median OS of 37.8 months. Median DFS and OS of down-staged patients were significantly longer than those of non-downstaged patients. The grade 4 toxicities during neoadjuvant chemotherapy were limited to neutropenia (2.9%) and vomiting (2.9%). Methods Patients with locally advanced ESCC (stage IIA to IIIC) and performance status 0-1 were enrolled and received two cycles of nab-paclitaxel (100 mg/m2) on day 1, 8, 22 and 29, and cisplatin (75 mg/m2) on day 1 and 22, followed by resection. Two cycles of adjuvant chemotherapy with the same regimen were given. Postoperative radiotherapy was permitted and decided by radiation therapist. Conclusion Weekly nab-paclitaxel with three-weekly cisplatin seems effective and safe as a neoadjuvant chemotherapy strategy for locally advanced ESCC. Down-staged patients have favorable outcome. ClinicalTrials.gov Identifier NCT01258192 PMID:27244882

Activation and Repression of Epstein-Barr Virus and Kaposi's Sarcoma-Associated Herpesvirus Lytic Cycles by Short- and Medium-Chain Fatty Acids

PubMed Central

Gorres, Kelly L.; Daigle, Derek; Mohanram, Sudharshan

2014-01-01

ABSTRACT The lytic cycles of Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) are induced in cell culture by sodium butyrate (NaB), a short-chain fatty acid (SCFA) histone deacetylase (HDAC) inhibitor. Valproic acid (VPA), another SCFA and an HDAC inhibitor, induces the lytic cycle of KSHV but blocks EBV lytic reactivation. To explore the hypothesis that structural differences between NaB and VPA account for their functional effects on the two related viruses, we investigated the capacity of 16 structurally related short- and medium-chain fatty acids to promote or prevent lytic cycle reactivation. SCFAs differentially affected EBV and KSHV reactivation. KSHV was reactivated by all SCFAs that are HDAC inhibitors, including phenylbutyrate. However, several fatty acid HDAC inhibitors, such as isobutyrate and phenylbutyrate, did not reactivate EBV. Reactivation of KSHV lytic transcripts could not be blocked completely by any fatty acid tested. In contrast, several medium-chain fatty acids inhibited lytic activation of EBV. Fatty acids that blocked EBV reactivation were more lipophilic than those that activated EBV. VPA blocked activation of the BZLF1 promoter by NaB but did not block the transcriptional function of ZEBRA. VPA also blocked activation of the DNA damage response that accompanies EBV lytic cycle activation. Properties of SCFAs in addition to their effects on chromatin are likely to explain activation or repression of EBV. We concluded that fatty acids stimulate the two related human gammaherpesviruses to enter the lytic cycle through different pathways. IMPORTANCE Lytic reactivation of EBV and KSHV is needed for persistence of these viruses and plays a role in carcinogenesis. Our direct comparison highlights the mechanistic differences in lytic reactivation between related human oncogenic gammaherpesviruses. Our findings have therapeutic implications, as fatty acids are found in the diet and produced by the human microbiota

The Subpolar North Atlantic Spring Bloom - What Did We Learn from the NAB 2008 Autonomous Experiment?

NASA Astrophysics Data System (ADS)

Perry, M. J.

2015-12-01

The subpolar North Atlantic bloom is one of the most remarkable features on the planet, with almost explosive 'greening' of the oceans. Over decades, investigators from countries bordering the North Atlantic have caught snippets of the bloom from research vessels or merchant ships transiting between continents. On 4 April 2008, Eric D'Asaro, Craig Lee, and I began a comprehensive study of the initiation and demise of the spring bloom using 2 types of autonomous platforms - a patch-following Lagrangian mixed-layer float and 4 float-following gliders. The 3 mo autonomous experiment integrated measurements from the float, gliders and ships, observations from satellites, and analyses from models. The diatom-dominated bloom began in mid April when the water column stabilized, not by solar warming, but rather by eddy-driven slumping of horizontal density gradients. The resulting bloom was patchy in both biomass and phytoplankton diversity, despite high, non-limiting concentrations of macronutrients. Magnitudes and relative proportions of net community productivity (NCP; determined from autonomous budgets of O2 and NO3) and net phytoplankton productivity (NPP; computed from ship-based photosynthetic parameters and float-based biomass and light) diverged as the bloom evolved, with higher fractions of particulate organic carbon (POC) consumed within the mixed layer as the bloom aged. Export productivity (EP; derived as the difference between NCP and accumulation rate of POC) was of similar magnitude during the May diatom bloom and the June picophytoplankton bloom. When silicic acid dropped to 1 μM, diatoms aggregated and sank; the deep flux event was dominated by resting spores of Chaetoceros. Although a short-lived event, it was ubiquitously observed by the 4 gliders and ship. An eddy-driven subduction event was likewise observed, indicating transport of otherwise non-sinking POC along isopycnals to depths of > 200 m. These striking export events reinforce the value of a

Phase II study of nab-paclitaxel in refractory small bowel adenocarcinoma and CpG island methylator phenotype (CIMP)-high colorectal cancer.

PubMed

Overman, M J; Adam, L; Raghav, K; Wang, J; Kee, B; Fogelman, D; Eng, C; Vilar, E; Shroff, R; Dasari, A; Wolff, R; Morris, J; Karunasena, E; Pisanic, R; Azad, N; Kopetz, S

2018-01-01

Hypermethylation of promoter CpG islands [CpG island methylator phenotype (CIMP)] represents a unique pathway for the development of colorectal cancer (CRC), characterized by lack of chromosomal instability and a low rate of adenomatous polyposis coli (APC) mutations, which have both been correlated with taxane resistance. Similarly, small bowel adenocarcinoma (SBA), a rare tumor, also has a low rate of APC mutations. This phase II study evaluated taxane sensitivity in SBA and CIMP-high CRC. The primary objective was Response Evaluation Criteria in Solid Tumors version 1.1 response rate. Eligibility included Eastern Cooperative Oncology Group performance status 0/1, refractory disease, and SBA or CIMP-high metastatic CRC. Nab-paclitaxel was initially administered at a dose of 260 mg/m2 every 3 weeks but was reduced to 220 mg/m2 owing to toxicity. A total of 21 patients with CIMP-high CRC and 13 with SBA were enrolled from November 2012 to October 2014. The efficacy-assessable population (patients who received at least three doses of the treatment) comprised 15 CIMP-high CRC patients and 10 SBA patients. Common grade 3 or 4 toxicities were fatigue (12%), neutropenia (9%), febrile neutropenia (9%), dehydration (6%), and thrombocytopenia (6%). No responses were seen in the CIMP-high CRC cohort and two partial responses were seen in the SBA cohort. Median progression-free survival was significantly greater in the SBA cohort than in the CIMP-high CRC cohort (3.2 months compared with 2.1 months, P = 0.03). Neither APC mutation status nor CHFR methylation status correlated with efficacy in the CIMP-high CRC cohort. In vivo testing of paclitaxel in an SBA patient-derived xenograft validated the activity of taxanes in this disease type. Although preclinical studies suggested taxane sensitivity was associated with chromosomal stability and wild-type APC, we found that nab-paclitaxel was inactive in CIMP-high metastatic CRC. Nab-paclitaxel may represent a novel

Acid-Base Homeostasis

PubMed Central

Nakhoul, Nazih; Hering-Smith, Kathleen S.

2015-01-01

Acid-base homeostasis and pH regulation are critical for both normal physiology and cell metabolism and function. The importance of this regulation is evidenced by a variety of physiologic derangements that occur when plasma pH is either high or low. The kidneys have the predominant role in regulating the systemic bicarbonate concentration and hence, the metabolic component of acid-base balance. This function of the kidneys has two components: reabsorption of virtually all of the filtered HCO3− and production of new bicarbonate to replace that consumed by normal or pathologic acids. This production or generation of new HCO3− is done by net acid excretion. Under normal conditions, approximately one-third to one-half of net acid excretion by the kidneys is in the form of titratable acid. The other one-half to two-thirds is the excretion of ammonium. The capacity to excrete ammonium under conditions of acid loads is quantitatively much greater than the capacity to increase titratable acid. Multiple, often redundant pathways and processes exist to regulate these renal functions. Derangements in acid-base homeostasis, however, are common in clinical medicine and can often be related to the systems involved in acid-base transport in the kidneys. PMID:26597304

Efficacy of severe acute respiratory syndrome vaccine based on a nonhuman primate adenovirus in the presence of immunity against human adenovirus.

PubMed

Zhi, Yan; Figueredo, Joanita; Kobinger, Gary P; Hagan, Heather; Calcedo, Roberto; Miller, James R; Gao, Guangping; Wilson, James M

2006-05-01

Replication-deficient human adenovirus type 5 (AdH5) vectors can induce strong transgene product-specific cellular and humoral responses. However, many adult humans have neutralizing antibodies (NAbs) against AdH5 as a result of natural infection with this virus. Therefore, a chimpanzee adenovirus C7 (AdC7) vector was developed to circumvent interference by preexisting immunity to AdH5. This study evaluated the impact of preexisting immunity to human adenovirus on the efficacy of adenovirus-based vaccines against the coronavirus that causes severe acute respiratory syndrome (SARS-CoV). Efficacy was assessed after intramuscular injection of the vector into mice and was measured as the frequency of SARS-CoV-specific T cells and NAbs against SARS-CoV. Immunogenicity of the AdH5-based vaccine was significantly attenuated or completely abolished when the preexisting anti-AdH5 NAb titer was higher than 40. Because 27% of human serum samples from the United States tested so far have an anti-AdH5 NAb titer higher than 40, our results suggested that a significant percentage of humans with preexisting anti-AdH5 immunity would not be candidates for vaccination with an AdH5-based genetic vaccine. In contrast, preexisting anti-AdH5 NAbs have a minimal effect on the potency of the AdC7-based genetic vaccine. Taken together, our studies warrant the further development of AdC7 as a vaccine carrier for human trials.

Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as second-line chemotherapy in HER2-negative, taxane-pretreated metastatic breast cancer patients: prospective evaluation of activity, safety, and quality of life.

PubMed

Palumbo, Raffaella; Sottotetti, Federico; Trifirò, Giuseppe; Piazza, Elena; Ferzi, Antonella; Gambaro, Anna; Spinapolice, Elena Giulia; Pozzi, Emma; Tagliaferri, Barbara; Teragni, Cristina; Bernardo, Antonio

2015-01-01

A prospective, multicenter trial was undertaken to assess the activity, safety, and quality of life of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as second-line chemotherapy in HER2-negative, taxane-pretreated metastatic breast cancer (MBC). Fifty-two women with HER2-negative MBC who were candidates for second-line chemotherapy for the metastatic disease were enrolled and treated at three centers in Northern Italy. All patients had previously received taxane-based chemotherapy in the adjuvant or first-line metastatic setting. Single-agent nab-paclitaxel was given at the dose of 260 mg/m(2) as a 30-minute intravenous infusion on day 1 each treatment cycle, which lasted 3 weeks, in the outpatient setting. No steroid or antihistamine premedication was provided. Treatment was stopped for documented disease progression, unacceptable toxicity, or patient refusal. All of the enrolled patients were evaluable for the study endpoints. The objective response rate was 48% (95% CI, 31.5%-61.3%) and included complete responses from 13.5%. Disease stabilization was obtained in 19 patients and lasted >6 months in 15 of them; the overall clinical benefit rate was 77%. The median time to response was 70 days (range 52-86 days). The median progression-free survival time was 8.9 months (95% CI, 8.0-11.6 months, range 5-21+ months). The median overall survival point has not yet been reached. Toxicities were expected and manageable with good patient compliance and preserved quality of life in patients given long-term treatment. Our results showed that single-agent nab-paclitaxel 260 mg/m(2) every 3 weeks is an effective and well tolerated regimen as second-line chemotherapy in HER2-negative, taxane-pretreated MBC patients, and that it produced interesting values of objective response rate and progression-free survival without the concern of significant toxicity. Specifically, the present study shows that such a regimen is a valid therapeutic option for that 'difficult to

The Acid-Base Titration of a Very Weak Acid: Boric Acid

ERIC Educational Resources Information Center

Celeste, M.; Azevedo, C.; Cavaleiro, Ana M. V.

2012-01-01

A laboratory experiment based on the titration of boric acid with strong base in the presence of d-mannitol is described. Boric acid is a very weak acid and direct titration with NaOH is not possible. An auxiliary reagent that contributes to the release of protons in a known stoichiometry facilitates the acid-base titration. Students obtain the…

Genetic variation of natural antibodies in milk of Dutch Holstein-Friesian cows.

PubMed

Ploegaert, T C W; Wijga, S; Tijhaar, E; van der Poel, J J; Lam, T J G M; Savelkoul, H F J; Parmentier, H K; van Arendonk, J A M

2010-11-01

Defense mechanisms of dairy cows against diseases partly rest on their naturally present disease resistance capacity. Natural antibodies (NAb) form a soluble part of the innate immune system, being defined as antibodies circulating in animals without prior intentional antigenic stimulation. Genetic selection on NAb titers in milk, therefore, might improve disease resistance. We estimated genetic parameters of NAb titers binding lipopolysaccharide, lipoteichoic acid (LTA), peptidoglycan, and keyhole limpet hemocyanin, and titers of the NAb isotypes IgG1, IgM, and IgA binding LTA in milk of Dutch Holstein-Friesian heifers. Natural antibody titers were measured in 1 milk sample from each of 1,939 Holstein-Friesian heifers and used for estimating genetic parameters of NAb titers. The data show that phenotypic variation exists among heifers in NAb titers binding lipopolysaccharide, LTA, peptidoglycan, and keyhole limpet hemocyanin, and the NAb isotypes IgG1, IgM, and IgA binding LTA in milk. High genetic correlations among NAb (ranging from 0.45 to 0.99) indicated a common genetic basis for the levels of different NAb in bovine milk. Intra-herd heritability estimates for NAb ranged from 0.10 to 0.53. The results indicated that NAb levels have potential for genetic selection. Copyright © 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

A Phase I Study of Hepatic Arterial Infusion of Nab-Paclitaxel in Combination with Intravenous Gemcitabine and Bevacizumab for Patients with Advanced Cancers and Predominant Liver Metastases

PubMed Central

Tsimberidou, Apostolia M.; Ye, Yang; Wheler, Jennifer; Naing, Aung; Hong, David; Nwosu, Uchechi; Hess, Kenneth R.; Wolff, Robert A.

2014-01-01

PURPOSE We conducted a Phase I clinical trial for patients with advanced cancer and predominant liver disease. EXPERIMENTAL DESIGN Patients were treated with HAI nab-paclitaxel (120-210 mg/m2; day 1); intravenous bevacizumab (10 mg/kg; day 1); and intravenous gemcitabine (600-800 mg/m2; days 1 and 8). A conventional “3 + 3” study design was used. RESULTS Fifty patients with advanced cancer and predominant liver metastases were treated (median age, 58 years; 27 women, 23 men; median number of prior therapies, 3 [range, 0-12]). The most common cancers were breast (n=9) and pancreatic (n=9). Overall, 264 cycles were administered (median/patient, 4; range, 1-17). No dose-limiting toxicities were noted during the escalation phase. On dose level 4, 3 patients were unable to receive gemcitabine on day 8 because of severe thrombocytopenia. Dose level 3 was selected as the maximum tolerated dose (HAI nab-paclitaxel 180 mg/m2 and intravenous gemcitabine 800 mg/m2 and bevacizumab 10 mg/kg); Thirty-two patients were treated in the expansion phase. The most common treatment-related toxicities were thrombocytopenia (n=17), neutropenia (n=10), and fatigue (n=12). Of 46 patients evaluable for response, 9 (20%) had a partial response [1] and 9 (20%) had stable disease for {greater than or equal to} 6 months. The median overall survival duration was 7.0 months (95% CI: 4, 22 months) and the median progression-free survival duration was 4.2 months (95% CI: 2.7, 8.6 months). CONCLUSIONS HAI nab-paclitaxel in combination with gemcitabine and bevacizumab was well tolerated and had antitumor activity in selected patients with advanced cancer and liver metastases. PMID:23377373

A novel cell-based assay for measuring neutralizing autoantibodies against type I interferons in patients with autoimmune polyendocrine syndrome type 1.

PubMed

Breivik, Lars; Oftedal, Bergithe E V; Bøe Wolff, Anette S; Bratland, Eirik; Orlova, Elizaveta M; Husebye, Eystein S

2014-07-01

An important characteristic of autoimmune polyendocrine syndrome type 1 (APS 1) is the existence of neutralizing autoantibodies (nAbs) against the type I interferons (IFN) -α2 and -ω at frequencies close to 100%. Type 1 IFN autoantibodies are detected by antiviral neutralizing assays (AVA), binding assays with radiolabelled antigens (RLBA), enzyme-linked immunosorbent assay (ELISA), or by reporter-based cell assays. We here present a simple and reliable version of the latter utilizing a commercially available cell line (HEK-Blue IFN-α/β). All 67 APS 1 patients were positive for IFN-ω nAbs, while 90% were positive for IFN-α2 nAbs, a 100% and 96% correlation with RLBA, respectively. All blood donors and non-APS 1 patients were negative. The dilution titer required to reduce the effect of IFN-ω nAbs correlated with the RLBA index. This cell-based autoantibody assay (CBAA) is easy to perform, suitable for high throughput, while providing high specificity and sensitivity. Copyright © 2014 Elsevier Inc. All rights reserved.

Nab-paclitaxel plus either gemcitabine or simplified leucovorin and fluorouracil as first-line therapy for metastatic pancreatic adenocarcinoma (AFUGEM GERCOR): a non-comparative, multicentre, open-label, randomised phase 2 trial.

PubMed

Bachet, Jean-Baptiste; Hammel, Pascal; Desramé, Jérôme; Meurisse, Aurélia; Chibaudel, Benoist; André, Thierry; Debourdeau, Philippe; Dauba, Jérome; Lecomte, Thierry; Seitz, Jean-François; Tournigand, Christophe; Aparicio, Thomas; Meyer, Véronique Guerin; Taieb, Julien; Volet, Julien; Monier, Amandine; Bonnetain, Franck; Louvet, Christophe

2017-05-01

Nab-paclitaxel plus gemcitabine has become a standard treatment regimen in patients with metastatic pancreatic adenocarcinoma; however, retrospective data suggest that gemcitabine might be inefficient in 50-60% of patients and thus not an optimum regimen in combination with nab-paclitaxel. We did a phase 2 trial to assess the activity and safety of a new regimen of nab-paclitaxel plus simplified leucovorin and fluorouracil. We did a non-comparative, multicentre, open-label, randomised phase 2 trial in 15 hospitals and institutions in France. Eligible participants were previously untreated patients with metastatic pancreatic adenocarcinoma (previous adjuvant chemotherapy after curative intent resection was allowed if the interval between the end of chemotherapy and relapse was more than 12 months). Patients had to have at least one measurable lesion assessed by CT scan or MRI and an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less. We randomly assigned participants (1:2) centrally to 28-day cycles of either gemcitabine plus nab-paclitaxel or simplified leucovorin and fluorouracil plus nab-paclitaxel. The randomisation was by minimisation, stratified by centre and ECOG performance status. Drugs were administered in each cycle as follows: nab-paclitaxel (125 mg/m 2 ) and gemcitabine (1000 mg/m 2 ) as 30-min intravenous infusions on days 1, 8, and 15; leucovorin (400 mg/m 2 ) as a 120-min intravenous infusion on days 1 and 15; and fluorouracil (400 mg/m 2 ) as a 5-min bolus intravenous infusion followed by a 46-h continuous intravenous infusion of 2400 mg/m 2 on days 1 and 15. Patients continued treatment until unacceptable toxicity, disease progression, or patient withdrawal. The primary endpoint was progression-free survival at 4 months in the first 72 assessable patients in the leucovorin and fluorouracil group, with a target of 50% for the regimen to be deemed sufficiently active to warrant further study. We did the primary analysis on the

Effect of a single oral dose of rabeprazole on nocturnal acid breakthrough and nocturnal alkaline amplitude

PubMed Central

Luo, Jin-Yan; Niu, Chun-Yan; Wang, Xue-Qin; Zhu, You-Ling; Gong, Jun

2003-01-01

AIM: To study the effect of rabeprazole (RAB) on nocturnal acid breakthrough (NAB) and nocturnal alkaline amplitude (NAKA) and to compare it with omeprazole (OME) and pantoprazole (PAN). METHODS: By an open comparative study, forty patients with active peptic ulcer were randomly assigned to receive one of the three PPIs (proton pump inhibitor) with a single oral dose. They were divided into RAB group (10 mg), OME group (20 mg) and PAN group (40 mg). Twenty healthy volunteers were enrolled to the control group (without taking any drug). Intragastric pH monitoring was then performed 1 h before and 24 h after the dose was given. RESULTS: No clinically undesirable signs and symptoms possibly attributed to the administration of RAB or OME and PAN were recognizable throughout the study period. All subjects completed the study according to the protocol. All data were processed by a computer using the Student t test or t’ test followed by an analysis of covariance. P < 0.05 was considered to have statistical significance. The intragastric pH of NAB was significantly higher in RAB group (1.84 ± 0.55) than in either OME group (1.15 ± 0.31) or PAN group (1.10 ± 0.30) (both P < 0.01). RAB produced a longer sustaining time (4.65 ± 1.22 h) on NAKA than OME (3.22 ± 1.89 h) (P < 0.05), PAN (3.15 ± 1.92 h) (P < 0.05), and the sustaining time of NAKA in RAB group was longer than that in the healthy control group (P < 0.01) too. In addition, RAB produced a much higher pH on NAKA (6.41 ± 0.45) in comparison with PAN (6.01 ± 0.92) (P < 0.05). CONCLUSION: A single oral dose of 10 mg RAB may increase the pH of NAB and shorten the sustaining time of NAB, and it may increase the pH of NAKA as well as prolong the sustaining time of NAKA. PMID:14606102

Bile acids. XLIV, quantitation of bile acids from the bile fistula rat given (4-14C) cholesterol.

PubMed

Siegfried, C M; Doisy, E A; Elliott, W H

1975-01-24

The bile acids derived from [4-14-C]cholesterol administered intracardially to rats with cannulated bile ducts were identified and quantitated. Over a period of 28 days about 90% of the administered 14-C was found in bile of which 73% was retained in the biliary acid fraction. [7beta-3-H]cholic acid, alpha-muri[3beta-3-H]cholic acid, beta-muri[3beta-3-H]cholic acid and litho[3beta-3-H]cholic acid were prepared with specific activities of about 30 muCi/mg by reduction of appropriate ketonic precursors with NaB3H4 and were added to the biliary acid fraction. After separation and purification of the bile acids, cholic, chenodeoxycholic, alpha- and beta-muricholic acids accounted for 70, 16, 7.5 and 6.1%, respectively, of the 14-C in the biliary acid fraction. The specific activities of these isolated 14-C-labeled acids were almost identical. Lithocholic acid accounted for a maximum of 0.2% and ursodeoxycholic acid and 7-oxolithocholic acid could account for no more than 2% of the biliary 14-C. Gas-liquid chromatography on 3% OV-17 of the trimethylsilyl ether derivatives of the methyl esters of the common bile acids of rat bile results in their complete separation and provides a convenient means of estimating the relative proportions of these acids in rat bile. By this method, the relative amounts of the four major acids, cholic, chenodeoxycholic, alpha- and beta-muricholic acids were 63, 20, 8 and 6%, respectively.

Population-based study of invasive disease due to beta-hemolytic streptococci of groups other than A and B.

PubMed

Broyles, Laura N; Van Beneden, Chris; Beall, Bernard; Facklam, Richard; Shewmaker, P Lynn; Malpiedi, Paul; Daily, Pamala; Reingold, Arthur; Farley, Monica M

2009-03-15

Beta-hemolytic streptococci of groups other than A and B (NABS) are increasingly recognized as causes of clinically significant disease, but precise information about this heterogeneous group is lacking. We report the incidence of NABS infection and describe the epidemiologic and clinical characteristics. Active, population-based surveillance for invasive NABS was performed over a 2-year period in the 8-county metropolitan Atlanta, Georgia, area and the 3-county San Francisco Bay, California, area. Clinical records were reviewed, and available isolates were sent to the Centers for Disease Control and Prevention (Atlanta) for additional microbiologic characterization. Incidences were calculated using year-appropriate US Census Bureau data. A total of 489 cases of invasive NABS infection were identified (3.2 cases per 100,000 population). The median age of patients was 55 years; 64% of patients were males, and 87% had underlying diseases. The incidence was higher among black persons than white persons (4.0 vs. 2.5 cases per 100,000 population; P < .01) and increased with age among all races. Infections were community acquired in 416 cases (85%). Among the 450 patients (94%) with NABS infection who were hospitalized, 55 (12%) died. Of 266 isolates (54%) speciated at the Centers for Disease Control and Prevention, 212 (80%) were Streptococcus dysgalactiae subspecies equisimilis; 46 (17%) were members of the Streptococcus anginosus group. S. dysgalactiae subspecies equisimilis primarily presented as skin and soft-tissue infection in older patients, whereas individuals with invasive S. anginosus group infections were more likely to be younger patients with intra-abdominal infections. NABS comprise multiple distinct species that cause a significant number of community-acquired invasive infections. Clinical manifestations differ by species. Thus, speciation of invasive NABS may be warranted in clinical settings.

On the acid-base properties of humic acid in soil.

PubMed

Cooke, James D; Hamilton-Taylor, John; Tipping, Edward

2007-01-15

Humic acid was isolated from three contrasting organic-rich soils and acid-base titrations performed over a range of ionic strengths. Results obtained were unlike most humic acid data sets; they showed a greater ionic strength dependency at low pH than at high pH. Forward- and back-titrations with the base and acid revealed hysteresis, particularly at low pH. Previous authors attributed this type of hysteresis to humic acid aggregates-created during the isolation procedure-being redissolved during titration as the pH increased and regarded the results as artificial. However, forward- and back-titrations with organic-rich soils also demonstrated a similar hysteretic behavior. These observations indicate (i) that titrations of humic acid in aggregated form (as opposed to the more usual dissolved form) are more representative of the acid-base properties of humic acid in soil and (ii) that the ionic strength dependency of proton binding in humic acid is related to its degree of aggregation. Thus, the current use of models based on data from dissolved humic substances to predictthe acid-base properties of humic acid in soil under environmental conditions may be flawed and could substantially overestimate their acid buffering capacity.

The first proton sponge-based amino acids: synthesis, acid-base properties and some reactivity.

PubMed

Ozeryanskii, Valery A; Gorbacheva, Anastasia Yu; Pozharskii, Alexander F; Vlasenko, Marina P; Tereznikov, Alexander Yu; Chernov'yants, Margarita S

2015-08-21

The first hybrid base constructed from 1,8-bis(dimethylamino)naphthalene (proton sponge or DMAN) and glycine, N-methyl-N-(8-dimethylamino-1-naphthyl)aminoacetic acid, was synthesised in high yield and its hydrobromide was structurally characterised and used to determine the acid-base properties via potentiometric titration. It was found that the basic strength of the DMAN-glycine base (pKa = 11.57, H2O) is on the level of amidine amino acids like arginine and creatine and its structure, zwitterionic vs. neutral, based on the spectroscopic (IR, NMR, mass) and theoretical (DFT) approaches has a strong preference to the zwitterionic form. Unlike glycine, the DMAN-glycine zwitterion is N-chiral and is hydrolytically cleaved with the loss of glycolic acid on heating in DMSO. This reaction together with the mild decarboxylative conversion of proton sponge-based amino acids into 2,3-dihydroperimidinium salts under air-oxygen was monitored with the help of the DMAN-alanine amino acid. The newly devised amino acids are unique as they combine fluorescence, strongly basic and redox-active properties.

Complexity in Acid-Base Titrations: Multimer Formation Between Phosphoric Acids and Imines.

PubMed

Malm, Christian; Kim, Heejae; Wagner, Manfred; Hunger, Johannes

2017-08-10

Solutions of Brønsted acids with bases in aprotic solvents are not only common model systems to study the fundamentals of proton transfer pathways but are also highly relevant to Brønsted acid catalysis. Despite their importance the light nature of the proton makes characterization of acid-base aggregates challenging. Here, we track such acid-base interactions over a broad range of relative compositions between diphenyl phosphoric acid and the base quinaldine in dichloromethane, by using a combination of dielectric relaxation and NMR spectroscopy. In contrast to what one would expect for an acid-base titration, we find strong deviations from quantitative proton transfer from the acid to the base. Even for an excess of the base, multimers consisting of one base and at least two acid molecules are formed, in addition to the occurrence of proton transfer from the acid to the base and simultaneous formation of ion pairs. For equimolar mixtures such multimers constitute about one third of all intermolecular aggregates. Quantitative analysis of our results shows that the acid-base association constant is only around six times larger than that for the acid binding to an acid-base dimer, that is, to an already protonated base. Our findings have implications for the interpretation of previous studies of reactive intermediates in organocatalysis and provide a rationale for previously observed nonlinear effects in phosphoric acid catalysis. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Synthesis of new kojic acid based unnatural α-amino acid derivatives.

PubMed

Balakrishna, C; Payili, Nagaraju; Yennam, Satyanarayana; Uma Devi, P; Behera, Manoranjan

2015-11-01

An efficient method for the preparation of kojic acid based α-amino acid derivatives by alkylation of glycinate schiff base with bromokojic acids have been described. Using this method, mono as well as di alkylated kojic acid-amino acid conjugates have been prepared. This is the first synthesis of C-linked kojic acid-amino acid conjugate where kojic acid is directly linked to amino acid through a C-C bond. Copyright © 2015 Elsevier Ltd. All rights reserved.

Age-, sex-, and education-specific norms for an extended CERAD Neuropsychological Assessment Battery-Results from the population-based LIFE-Adult-Study.

PubMed

Luck, Tobias; Pabst, Alexander; Rodriguez, Francisca S; Schroeter, Matthias L; Witte, Veronica; Hinz, Andreas; Mehnert, Anja; Engel, Christoph; Loeffler, Markus; Thiery, Joachim; Villringer, Arno; Riedel-Heller, Steffi G

2018-05-01

To provide new age-, sex-, and education-specific reference values for an extended version of the well-established Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery (CERAD-NAB) that additionally includes the Trail Making Test and the Verbal Fluency Test-S-Words. Norms were calculated based on the cognitive performances of n = 1,888 dementia-free participants (60-79 years) from the population-based German LIFE-Adult-Study. Multiple regressions were used to examine the association of the CERAD-NAB scores with age, sex, and education. In order to calculate the norms, quantile and censored quantile regression analyses were performed estimating marginal means of the test scores at 2.28, 6.68, 10, 15.87, 25, 50, 75, and 90 percentiles for age-, sex-, and education-specific subgroups. Multiple regression analyses revealed that younger age was significantly associated with better cognitive performance in 15 CERAD-NAB measures and higher education with better cognitive performance in all 17 measures. Women performed significantly better than men in 12 measures and men than women in four measures. The determined norms indicate ceiling effects for the cognitive performances in the Boston Naming, Word List Recognition, Constructional Praxis Copying, and Constructional Praxis Recall tests. The new norms for the extended CERAD-NAB will be useful for evaluating dementia-free German-speaking adults in a broad variety of relevant cognitive domains. The extended CERAD-NAB follows more closely the criteria for the new DSM-5 Mild and Major Neurocognitive Disorder. Additionally, it could be further developed to include a test for social cognition. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Clinical roundtable monograph: Recent advances in taxanes for the first-line treatment of advanced non-small cell lung cancer.

PubMed

Socinski, Mark A; Govindan, Ramaswamy; Spigel, David

2012-10-01

Treatments for non-small cell lung cancer (NSCLC) are based on the broad categories of squamous or non-squamous histology. Frontline treatment options include pemetrexed and cisplatin, pemetrexed and a taxane, gemcitabine with cisplatin, and the addition of bevacizumab to a taxane and carboplatin. Pemetrexed is used for maintenance therapy for non-squamous NSCLC, whereas patients with squamous NSCLC lack easy options for maintenance therapy. nab-Paclitaxel overcomes the solubility and toxicity issues of solvent-based paclitaxel, and the albumin in nab-paclitaxel improves the concentration of the drug in the tumor. A recent phase III trial in NSCLC compared nab-paclitaxel with carboplatin versus solvent-based paclitaxel with carboplatin, and found improved overall response rates (ORRs) in the nab-paclitaxel arm (33% vs 25%; P=.005). In a subset analysis, NSCLC patients with squamous histology had a higher ORR (41%) with nab-paclitaxel than with solvent-based paclitaxel (24%; P<.001). Another subset analysis found that patients ages 70 years and older had improved overall survival (median 19.9 months) with nab-paclitaxel compared with solvent-based paclitaxel (median 10.4 months; P=.009). Patients in the nab-paclitaxel arm had less neuropathy, less hearing loss, and fewer interruptions in daily living than patients in the solvent-based paclitaxel arm.

Sodium Butyrate Inhibits Colorectal Cancer Cell Migration by Downregulating Bmi-1 Through Enhanced miR-200c Expression.

PubMed

Xu, Zhiyao; Tao, Jingjing; Chen, Ping; Chen, Long; Sharma, Sherven; Wang, Guanyu; Dong, Qinghua

2018-03-01

Short-chain fatty acid sodium butyrate (NaB) is the byproduct of bacterial anaerobic fermentation of dietary fiber in the colon, and has been shown to have an antitumor effect on colorectal cancer (CRC). The miR-200 family is a key regulator of the epithelial-mesenchymal transition (EMT). We investigate the role of miR-200s expression on cell migration in NaB-treated CRC cells. HCT116 and LOVO CRC cells treated with NaB depicted reduced cell proliferation, enhanced apoptosis, and cell cycle arrest. NaB inhibited cell migration in the wound healing and transwell assays, and in spheriod cultures while regulating EMT-related protein expression. NaB reciprocally increased miR-200s but reduced expression of their target genes (Bmi-1, Zeb1, EZH2). Cells transfected with miR-200c shRNA displayed a significant blockade of NaB-induced anti-invasive activity. Upregulation of Bmi-1 expression partially reversed the effect of NaB. In addition to inhibition of tumor growth in vivo, qRT-PCR results showed that NaB increased miR-200c/200b/492 expression in the tumor tissues. Immunohistochemistry and Western blotting results demonstrated that NaB decreased Bmi-1 expression in vivo. NaB inhibits CRC cell migration by enhancing miR-200c expression-mediated downregulation of Bmi-1. These findings support the utility of NaB in colorectal cancer therapy. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Development and validation of cell-based luciferase reporter gene assays for measuring neutralizing anti-drug antibodies against interferon beta.

PubMed

Hermanrud, Christina; Ryner, Malin; Luft, Thomas; Jensen, Poul Erik; Ingenhoven, Kathleen; Rat, Dorothea; Deisenhammer, Florian; Sørensen, Per Soelberg; Pallardy, Marc; Sikkema, Dan; Bertotti, Elisa; Kramer, Daniel; Creeke, Paul; Fogdell-Hahn, Anna

2016-03-01

Neutralizing anti-drug antibodies (NAbs) against therapeutic interferon beta (IFNβ) in people with multiple sclerosis (MS) are measured with cell-based bioassays. The aim of this study was to redevelop and validate two luciferase reporter-gene bioassays, LUC and iLite, using a cut-point approach to identify NAb positive samples. Such an approach is favored by the pharmaceutical industry and governmental regulatory agencies as it has a clear statistical basis and overcomes the limitations of the current assays based on the Kawade principle. The work was conducted following the latest assay guidelines. The assays were re-developed and validated as part of the "Anti-Biopharmaceutical Immunization: Prediction and analysis of clinical relevance to minimize the risk" (ABIRISK) consortium and involved a joint collaboration between four academic laboratories and two pharmaceutical companies. The LUC assay was validated at Innsbruck Medical University (LUCIMU) and at Rigshospitalet (LUCRH) Copenhagen, and the iLite assay at Karolinska Institutet, Stockholm. For both assays, the optimal serum sample concentration in relation to sensitivity and recovery was 2.5% (v/v) in assay media. A Shapiro-Wilk test indicated a normal distribution for the majority of runs, allowing a parametric approach for cut-point calculation to be used, where NAb positive samples could be identified with 95% confidence. An analysis of means and variances indicated that a floating cut-point should be used for all assays. The assays demonstrated acceptable sensitivity for being cell-based assays, with a confirmed limit of detection in neat serum of 1519 ng/mL for LUCIMU, 814 ng/mL for LUCRH, and 320 ng/mL for iLite. Use of the validated cut-point assay, in comparison with the previously used Kawade method, identified 14% more NAb positive samples. In conclusion, implementation of the cut-point design resulted in increased sensitivity to detect NAbs. However, the clinical significance of these low

Sequential injection redox or acid-base titration for determination of ascorbic acid or acetic acid.

PubMed

Lenghor, Narong; Jakmunee, Jaroon; Vilen, Michael; Sara, Rolf; Christian, Gary D; Grudpan, Kate

2002-12-06

Two sequential injection titration systems with spectrophotometric detection have been developed. The first system for determination of ascorbic acid was based on redox reaction between ascorbic acid and permanganate in an acidic medium and lead to a decrease in color intensity of permanganate, monitored at 525 nm. A linear dependence of peak area obtained with ascorbic acid concentration up to 1200 mg l(-1) was achieved. The relative standard deviation for 11 replicate determinations of 400 mg l(-1) ascorbic acid was 2.9%. The second system, for acetic acid determination, was based on acid-base titration of acetic acid with sodium hydroxide using phenolphthalein as an indicator. The decrease in color intensity of the indicator was proportional to the acid content. A linear calibration graph in the range of 2-8% w v(-1) of acetic acid with a relative standard deviation of 4.8% (5.0% w v(-1) acetic acid, n=11) was obtained. Sample throughputs of 60 h(-1) were achieved for both systems. The systems were successfully applied for the assays of ascorbic acid in vitamin C tablets and acetic acid content in vinegars, respectively.

The Conjugate Acid-Base Chart.

ERIC Educational Resources Information Center

Treptow, Richard S.

1986-01-01

Discusses the difficulties that beginning chemistry students have in understanding acid-base chemistry. Describes the use of conjugate acid-base charts in helping students visualize the conjugate relationship. Addresses chart construction, metal ions, buffers and pH titrations, and the organic functional groups and nonaqueous solvents. (TW)

Impact of SPARC expression on outcome in patients with advanced pancreatic cancer not receiving nab-paclitaxel: a pooled analysis from prospective clinical and translational trials

PubMed Central

Ormanns, Steffen; Haas, Michael; Baechmann, Sibylle; Altendorf-Hofmann, Annelore; Remold, Anna; Quietzsch, Detlef; Clemens, Michael R; Bentz, Martin; Geissler, Michael; Lambertz, Helmut; Kruger, Stephan; Kirchner, Thomas; Heinemann, Volker; Boeck, Stefan

2016-01-01

Background: Conflicting results on the role of secreted protein acidic and rich in cysteins (SPARC) expression have been reported in resected pancreatic ductal adenocarcinoma (PDAC), and its prognostic and/or predictive role in advanced PDAC (aPDAC) has not been extensively investigated yet. This study was designed to evaluate SPARC expression as a biomarker in aPDAC patients (pts) not receiving nab-paclitaxel. Methods: Using immunohistochemistry, we examined the stromal as well as the tumoral (i.e., cytoplasmic) SPARC expression in tumour tissue (primary tumours and metastases) of 134 aPDAC pts participating in completed prospective clinical and biomarker trials. The SPARC expression levels were correlated to the pts' clinicopathological parameters and survival times. Results: Sixty-seven per cent of the analysed tumours showed high stromal SPARC expression, which was not associated with overall survival (OS, median 9.1 vs 7.6 months, P=0.316). A positive cytoplasmic SPARC expression was detected in 55% of the tumours and correlated significantly with inferior progression-free survival (PFS, 6.2 vs 8.6 months, P=0.004) and OS (7.8 vs 8.4 months, P=0.032). This association was strongest for pts, where primary tumour tissue was examined (PFS: 6.7 vs 10.8 months, P=0.004; OS: 7.9 vs 11.9 months, P=0.030), whereas no significant correlation was detected for pts, where only metastatic tissue was available (PFS: 5.8 vs 6.6 months, P=0.502; OS: 7.0 vs 7.8 months, P=0.452). In pts receiving gemcitabine-based chemotherapy cytoplasmic SPARC expression was significantly associated with an inferior PFS and OS (PFS: 6.2 vs 9.2 months, P=0.002; OS 7.3 vs 9.9 months, P=0.012), whereas no such association was detected for stromal SPARC expression or for pts receiving fluoropyrimidine-based chemotherapy. Conclusion: We identified cytoplasmic SPARC expression in the primary tumour as a biomarker associated with inferior PFS and OS in aPDAC. Cytoplasmic SPARC expression may

Disorders of Acid-Base Balance: New Perspectives

PubMed Central

Seifter, Julian L.; Chang, Hsin-Yun

2017-01-01

Background Disorders of acid-base involve the complex interplay of many organ systems including brain, lungs, kidney, and liver. Compensations for acid-base disturbances within the brain are more complete, while limitations of compensations are more apparent for most systemic disorders. However, some of the limitations on compensations are necessary to survival, in that preservation of oxygenation, energy balance, cognition, electrolyte, and fluid balance are connected mechanistically. Summary This review aims to give new and comprehensive perspective on understanding acid-base balance and identifying associated disorders. All metabolic acid-base disorders can be approached in the context of the relative losses or gains of electrolytes or a change in the anion gap in body fluids. Acid-base and electrolyte balance are connected not only at the cellular level but also in daily clinical practice. Urine chemistry is essential to understanding electrolyte excretion and renal compensations. Key Messages Many constructs are helpful to understand acid-base, but these models are not mutually exclusive. Electroneutrality and the close interconnection between electrolyte and acid-base balance are important concepts to apply in acid-base diagnoses. All models have complexity and shortcuts that can help in practice. There is no reason to dismiss any of the present constructs, and there is benefit in a combined approach. PMID:28232934

Natural antibodies to glycans.

PubMed

Bovin, N V

2013-07-01

A wide variety of so-called natural antibodies (nAbs), i.e. immunoglobulins generated by B-1 cells, are directed to glycans. nAbs to glycans can be divided in three groups: 1) conservative nAbs, i.e. practically the same in all healthy donors with respect to their epitope specificity and level in blood; 2) allo-antibodies to blood group antigens; 3) plastic antibodies related to the first or the second group but discussed separately because their level changes considerably during diseases and some temporary conditions, in particular inflammation and pregnancy. Antibodies from the third group proved to be prospective markers of a number of diseases, whereas their unusual level (below or above the norm) is not necessarily the consequence of disease/state. Modern microarrays allowed the determination of the human repertoire, which proved to be unexpectedly broad. It was observed that the content of some nAbs reaches about 0.1% of total immunoglobulins. Immunoglobulins of M class dominate for most nAbs, constituting up to 80-90%. Their affinity (to a monovalent glycan, in KD terms) were found to be within the range 10(-4)-10(-6) M. Antibodies to Galβ1-3GlcNAc (Le(C)), 4-HSO3Galβ1-4GalNAc (4'-O-SuLN), Fucα1-3GlcNAc, Fucα1-4GlcNAc, GalNAcα1-3Gal (Adi), Galα1-4Galβ1-4Glc (P(k)), Galα1-4Galβ1-4GlcNAc (P1), GlcNAcα-terminated glycans, and hyaluronic acid should be noted among the nAbs revealed and studied during the last decade. At the same time, a kind of "taboo" is observed for a number of glycans: antibodies to Le(X) and Le(Y), and almost all gangliosides have not been observed in healthy persons. Many of the revealed nAbs were directed to constrained inner (core) part of glycan, directly adjoined to lipid of cell membrane or protein. The biological function of these nAbs remains unclear; for anti-core antibodies, a role of surveillance on appearance of aberrant, especially cancer, antigens is supposed. The first data related to oncodiagnostics based on

A Computer-Based Simulation of an Acid-Base Titration

ERIC Educational Resources Information Center

Boblick, John M.

1971-01-01

Reviews the advantages of computer simulated environments for experiments, referring in particular to acid-base titrations. Includes pre-lab instructions and a sample computer printout of a student's use of an acid-base simulation. Ten references. (PR)

Nucleic acid-based electrochemical nanobiosensors.

PubMed

Abi, Alireza; Mohammadpour, Zahra; Zuo, Xiaolei; Safavi, Afsaneh

2018-04-15

The detection of biomarkers using sensitive and selective analytical devices is critically important for the early stage diagnosis and treatment of diseases. The synergy between the high specificity of nucleic acid recognition units and the great sensitivity of electrochemical signal transductions has already shown promise for the development of efficient biosensing platforms. Yet nucleic-acid based electrochemical biosensors often rely on target amplification strategies (e.g., polymerase chain reactions) to detect analytes at clinically relevant concentration ranges. The complexity and time-consuming nature of these amplification methods impede moving nucleic acid-based electrochemical biosensors from laboratory-based to point-of-care test settings. Fortunately, advancements in nanotechnology have provided growing evidence that the recruitment of nanoscaled materials and structures can enhance the biosensing performance (particularly in terms of sensitivity and response time) to the level suitable for use in point-of-care diagnostic tools. This Review highlights the significant progress in the field of nucleic acid-based electrochemical nanobiosensing with the focus on the works published during the last five years. Copyright © 2017. Published by Elsevier B.V.

Investigating Students' Reasoning about Acid-Base Reactions

ERIC Educational Resources Information Center

Cooper, Melanie M.; Kouyoumdjian, Hovig; Underwood, Sonia M.

2016-01-01

Acid-base chemistry is central to a wide range of reactions. If students are able to understand how and why acid-base reactions occur, it should provide a basis for reasoning about a host of other reactions. Here, we report the development of a method to characterize student reasoning about acid-base reactions based on their description of…

Fluorescent sensors based on boronic acids

NASA Astrophysics Data System (ADS)

Cooper, Christopher R.; James, Tony D.

1999-05-01

Sensor systems have long been needed for detecting the presence in solution of certain chemically or biologically important species. Sensors are used in a wide range of applications from simple litmus paper that shows a single color change in acidic or basic environments to complex biological assays that use enzymes, antibodies and antigens to display binding events. With this work the use of boronic acids in the design and synthesis of sensors for saccharides (diols) will be presented. The fluorescent sensory systems rely on photoinduced electron transfer (PET) to modulate the observed fluorescence. When saccharides form cyclic boronate esters with boronic acids, the Lewis acidity of the boronic acid is enhanced and therefore the Lewis acid-base interaction between the boronic acid and a neighboring amine is strengthened. The strength of this acid-base interaction modulates the PET from the amine (acting as a quencher) to anthracene (acting as a fluorophore). These compounds show increased fluorescence at neutral pH through suppression of the PET from nitrogen to anthracene on saccharide binding. The general strategy for the development of saccharide selective systems will be discussed. The potential of the boronic acid based systems will be illustrated using the development of glucose and glucosamine selective fluorescent sensors as examples.

Ultrastructural observation of the acid-base resistant zone of all-in-one adhesives using three different acid-base challenges.

PubMed

Tsujimoto, Miho; Nikaido, Toru; Inoue, Go; Sadr, Alireza; Tagami, Junji

2010-11-01

The aim of this study was to analyze the ultrastructure of the dentin-adhesive interface using two all-in-one adhesive systems (Clearfil Tri-S Bond, TB; Tokuyama Bond Force, BF) after different acid-base challenges. Three solutions were used as acidic solutions for the acid-base challenges: a demineralizing solution (DS), a phosphoric acid solution (PA), and a hydrochloric acid solution (HCl). After the acid-base challenges, the bonded interfaces were examined by scanning electron microscopy. Thickness of the acid-base resistant zone (ABRZ) created in PA and HCl was thinner than in DS for both adhesive systems. For BF adhesive, an eroded area was observed beneath the ABRZ after immersion in PA and HCl, but not in DS. Conversely for TB adhesive, the eroded area was observed only after immersion in PA. In conclusion, although the ABRZ was observed for both all-in-one adhesive systems, its morphological features were influenced by the ingredients of both the adhesive material and acidic solution.

Primer on clinical acid-base problem solving.

PubMed

Whittier, William L; Rutecki, Gregory W

2004-03-01

Acid-base problem solving has been an integral part of medical practice in recent generations. Diseases discovered in the last 30-plus years, for example, Bartter syndrome and Gitelman syndrome, D-lactic acidosis, and bulimia nervosa, can be diagnosed according to characteristic acid-base findings. Accuracy in acid-base problem solving is a direct result of a reproducible, systematic approach to arterial pH, partial pressure of carbon dioxide, bicarbonate concentration, and electrolytes. The 'Rules of Five' is one tool that enables clinicians to determine the cause of simple and complex disorders, even triple acid-base disturbances, with consistency. In addition, other electrolyte abnormalities that accompany acid-base disorders, such as hypokalemia, can be incorporated into algorithms that complement the Rules and contribute to efficient problem solving in a wide variety of diseases. Recently urine electrolytes have also assisted clinicians in further characterizing select disturbances. Acid-base patterns, in many ways, can serve as a 'common diagnostic pathway' shared by all subspecialties in medicine. From infectious disease (eg, lactic acidemia with highly active antiviral therapy therapy) through endocrinology (eg, Conn's syndrome, high urine chloride alkalemia) to the interface between primary care and psychiatry (eg, bulimia nervosa with multiple potential acid-base disturbances), acid-base problem solving is the key to unlocking otherwise unrelated diagnoses. Inasmuch as the Rules are clinical tools, they are applied throughout this monograph to diverse pathologic conditions typical in contemporary practice.

Teaching Acid/Base Physiology in the Laboratory

ERIC Educational Resources Information Center

Friis, Ulla G.; Plovsing, Ronni; Hansen, Klaus; Laursen, Bent G.; Wallstedt, Birgitta

2010-01-01

Acid/base homeostasis is one of the most difficult subdisciplines of physiology for medical students to master. A different approach, where theory and practice are linked, might help students develop a deeper understanding of acid/base homeostasis. We therefore set out to develop a laboratory exercise in acid/base physiology that would provide…

Functional Conservation of the Transportin Nuclear Import Pathway in Divergent Organisms

PubMed Central

Siomi, Mikiko C.; Fromont, Micheline; Rain, Jean-Christophe; Wan, Lili; Wang, Fan; Legrain, Pierre; Dreyfuss, Gideon

1998-01-01

Human transportin1 (hTRN1) is the nuclear import receptor for a group of pre-mRNA/mRNA-binding proteins (heterogeneous nuclear ribonucleoproteins [hnRNP]) represented by hnRNP A1, which shuttle continuously between the nucleus and the cytoplasm. hTRN1 interacts with the M9 region of hnRNP A1, a 38-amino-acid domain rich in Gly, Ser, and Asn, and mediates the nuclear import of M9-bearing proteins in vitro. Saccharomyces cerevisiae transportin (yTRN; also known as YBR017c or Kap104p) has been identified and cloned. To understanding the nuclear import mediated by yTRN, we searched with a yeast two-hybrid system for proteins that interact with it. In an exhaustive screen of the S. cerevisiae genome, the most frequently selected open reading frame was the nuclear mRNA-binding protein, Nab2p. We delineated a ca.-50-amino-acid region in Nab2p, termed NAB35, which specifically binds yTRN and is similar to the M9 motif. NAB35 also interacts with hTRN1 and functions as a nuclear localization signal in mammalian cells. Interestingly, yTRN can also mediate the import of NAB35-bearing proteins into mammalian nuclei in vitro. We also report on additional substrates for TRN as well as sequences of Drosophila melanogaster, Xenopus laevis, and Schizosaccharomyces pombe TRNs. Together, these findings demonstrate that both the M9 signal and the nuclear import machinery utilized by the transportin pathway are conserved in evolution. PMID:9632798

[Kidney, Fluid, and Acid-Base Balance].

PubMed

Shioji, Naohiro; Hayashi, Masao; Morimatsu, Hiroshi

2016-05-01

Kidneys play an important role to maintain human homeostasis. They contribute to maintain body fluid, electrolytes, and acid-base balance. Especially in fluid control, we, physicians can intervene body fluid balance using fluid resuscitation and diuretics. In recent years, one type of fluid resuscitation, hydroxyl ethyl starch has been extensively studied in the field of intensive care. Although their effects on fluid resuscitation are reasonable, serious complications such as kidney injury requiring renal replacement therapy occur frequently. Now we have to pay more attention to this important complication. Another topic of fluid management is tolvaptan, a selective vasopressin-2 receptor antagonist Recent randomized trial suggested that tolvaptan has a similar supportive effect for fluid control and more cost effective compared to carperitide. In recent years, Stewart approach is recognized as one important tool to assess acid-base balance in critically ill patients. This approach has great value, especially to understand metabolic components in acid-base balance. Even for assessing the effects of kidneys on acid-base balance, this approach gives us interesting insight. We should appropriately use this new approach to treat acid-base abnormality in critically ill patients.

Nano albumin bound-paclitaxel in pancreatic cancer: Current evidences and future directions

PubMed Central

Giordano, Guido; Pancione, Massimo; Olivieri, Nunzio; Parcesepe, Pietro; Velocci, Marianna; Di Raimo, Tania; Coppola, Luigi; Toffoli, Giuseppe; D’Andrea, Mario Rosario

2017-01-01

Pancreatic cancer (PDAC) is an aggressive and chemoresistant disease, representing the fourth cause of cancer related deaths in western countries. Majority of patients have unresectable, locally advanced or metastatic disease at time of diagnosis and the 5-year survival rate in these conditions is extremely low. For more than a decade gemcitabine has been the cornerstone of metastatic PDAC treatment, although survival benefit was very poor. PDAC cells are surrounded by an intense desmoplastic reaction that may create a barrier to the drugs penetration within the tumor. Recently PDAC stroma has been addressed as a potential therapeutic target. Nano albumin bound (Nab)-paclitaxel is an innovative molecule depleting tumor stroma, through interaction between albumin and secreted protein acidic and rich in cysteine. Addition of nab-paclitaxel to gemcitabine has showed activity and efficacy in metastatic PDAC first-line treatment improving survival and overall response rate vs gemcitabine alone in the MPACT phase III study. This combination represents one of the standards of care in advanced PDAC therapy and is suitable to a broader spectrum of patients compared to other schedules. Nab-paclitaxel is under investigation as a backbone of chemotherapy in novel combinations with target agents or immunotherapy in locally advanced or metastatic PDAC. In this article, we provide an updated and critical overview about the role of nab-paclitaxel in PDAC treatment based on the latest advances in preclinical and clinical research. Furthermore, we focus on the use of nab-paclitaxel within the context of metastatic PDAC treatment landscape and we discuss about future implications in the light of current clinical ongoing trials. PMID:28932079

Novel Polymyxin Derivatives Carrying Only Three Positive Charges Are Effective Antibacterial Agents ▿

PubMed Central

Vaara, Martti; Fox, John; Loidl, Günther; Siikanen, Osmo; Apajalahti, Juha; Hansen, Frank; Frimodt-Møller, Niels; Nagai, Junya; Takano, Mikihisa; Vaara, Timo

2008-01-01

The lack of novel antibiotics against gram-negative bacteria has reinstated polymyxins as the drugs of last resort to treat serious infections caused by extremely multiresistant gram-negative organisms. However, polymyxins are nephrotoxic, and this feature may complicate therapy or even require its discontinuation. Like that of aminoglycosides, the nephrotoxicity of polymyxins might be related to the highly cationic nature of the molecule. Colistin and polymyxin B carry five positive charges. Here we show that novel polymyxin derivatives carrying only three positive charges are effective antibacterial agents. NAB739 has a cyclic peptide portion identical to that of polymyxin B, but in the linear portion of the peptide, it carries the threonyl-d-serinyl residue (no cationic charges) instead of the diaminobutyryl-threonyl-diaminobutyryl residue (two cationic charges). The MICs of NAB739 for 17 strains of Escherichia coli were identical, or very close, to those of polymyxin B. Furthermore, NAB739 was effective against other polymyxin-susceptible strains of Enterobacteriaceae and against Acinetobacter baumannii. At subinhibitory concentrations, it dramatically sensitized A. baumannii to low concentrations of antibiotics such as rifampin, clarithromycin, vancomycin, fusidic acid, and meropenem. NAB739 methanesulfonate was a prodrug analogous to colistin methanesulfonate. NAB740 was the most active derivative against Pseudomonas aeruginosa. NAB7061 (linear portion of the peptide, threonyl-aminobutyryl) lacked direct antibacterial activity but sensitized the targets to hydrophobic antibiotics by factors up to 2,000. The affinities of the NAB compounds for isolated rat kidney brush border membrane were significantly lower than that of polymyxin B. PMID:18591267

Whole body acid-base modeling revisited.

PubMed

Ring, Troels; Nielsen, Søren

2017-04-01

The textbook account of whole body acid-base balance in terms of endogenous acid production, renal net acid excretion, and gastrointestinal alkali absorption, which is the only comprehensive model around, has never been applied in clinical practice or been formally validated. To improve understanding of acid-base modeling, we managed to write up this conventional model as an expression solely on urine chemistry. Renal net acid excretion and endogenous acid production were already formulated in terms of urine chemistry, and we could from the literature also see gastrointestinal alkali absorption in terms of urine excretions. With a few assumptions it was possible to see that this expression of net acid balance was arithmetically identical to minus urine charge, whereby under the development of acidosis, urine was predicted to acquire a net negative charge. The literature already mentions unexplained negative urine charges so we scrutinized a series of seminal papers and confirmed empirically the theoretical prediction that observed urine charge did acquire negative charge as acidosis developed. Hence, we can conclude that the conventional model is problematic since it predicts what is physiologically impossible. Therefore, we need a new model for whole body acid-base balance, which does not have impossible implications. Furthermore, new experimental studies are needed to account for charge imbalance in urine under development of acidosis. Copyright © 2017 the American Physiological Society.

The effect of a mixture of dairy-based feed ingredients, vegetable fats, and yeast cell walls on performance and innate immunity of weaned piglets.

PubMed

Gerritsen, R; Klaassen, G J; Schuttert, G; Rouwers, S M G; Parmentier, H K; Molist, F

2012-12-01

Positive effects of yeast concentrate on immunity and performance of weaned piglets have been reported. However, the effects on innate immunity were not examined. Natural antibodies (NAb) are part of innate immunity and have been related to health and survival in fish, poultry, rodents, and man. Yeast cell walls may also affect innate immunity of weaned piglets. We studied the effect of Nuklospray ProHealth containing a spray dried blend of dairy-based feed ingredients, vegetable fats, and processed yeast cell walls as protein source on NAb levels and performance of weaned piglets. A total of 120 piglets weaned at 28 d of age were assigned 2 treatments comprising a control diet and an experimental diet with the test product. Piglets were housed in groups of 6 during the first 4 weeks after weaning. Blood samples of 20 healthy nonmedicated piglets per treatment were taken at days 0, 14, and 28 after weaning and analyzed for NAb levels binding keyhole limpet hemocyanin by an indirect ELISA procedure. Performance parameters also were determined. Overall, the experimental diet tended to improve feed intake (574 vs. 522 g/d; P < 0.1), ADG (449 vs. 412 g/d; P < 0.1), and final BW (21.4 vs. 20.3 kg; P = 0.08) compared to the control diet. No differences were found in feed conversion ratio or fecal score. At day 0, no differences in NAb levels were found, but on day 14 after weaning, NAb levels of piglets fed the experimental diet were significantly higher than of piglets fed the control diet (2.05 vs. 1.70; P < 0.05). On day 28 after weaning no differences were found. These results indicate that day 14 postweaning levels of NAb as a parameter of innate immunity were improved and indicate a tendency for improvement of postweaning performance of piglets fed diets supplemented with Nuklospray ProHealth.

Quantification of Lewis acid induced Brønsted acidity of protogenic Lewis bases.

PubMed

Lathem, A Paige; Heiden, Zachariah M

2017-05-09

Proton transfer promoted by the coordination of protogenic Lewis bases to a Lewis acid is a critical step in catalytic transformations. Although the acidification of water upon coordination to a Lewis acid has been known for decades, no attempts have been made to correlate the Brønsted acidity of the coordinated water molecule with Lewis acid strength. To probe this effect, the pK a 's (estimated error of 1.3 pK a units) in acetonitrile of ten protogenic Lewis bases coordinated to seven Lewis acids containing Lewis acidities varying 70 kcal mol -1 , were computed. To quantify Lewis acid strength, the ability to transfer a hydride (hydride donor ability) from the respective main group hydride was used. Coordination of a Lewis acid to water increased the acidity of the bound water molecule between 20 and 50 pK a units. A linear correlation exhibiting a 2.6 pK a unit change of the Lewis acid-water adduct per ten kcal mol -1 change in hydride donor ability of the respective main group hydride was obtained. For the ten protogenic Lewis bases studied, the coordinated protogenic Lewis bases were acidified between 10 and 50 pK a units. On average, a ten kcal mol -1 change in hydride donor ability of the respective main group hydride resulted in about a 2.8 pK a unit change in the Brønsted acidity of the Lewis acid-Lewis base adducts. Since attempts to computationally investigate the pK a of main group dihydrogen complexes were unsuccessful, experimental determination of the first reported pK a of a main group dihydrogen complex is described. The pK a of H 2 -B(C 6 F 5 ) 3 was determined to be 5.8 ± 0.2 in acetonitrile.

General base-general acid catalysis by terpenoid cyclases.

PubMed

Pemberton, Travis A; Christianson, David W

2016-07-01

Terpenoid cyclases catalyze the most complex reactions in biology, in that more than half of the substrate carbon atoms often undergo changes in bonding during the course of a multistep cyclization cascade that proceeds through multiple carbocation intermediates. Many cyclization mechanisms require stereospecific deprotonation and reprotonation steps, and most cyclization cascades are terminated by deprotonation to yield an olefin product. The first bacterial terpenoid cyclase to yield a crystal structure was pentalenene synthase from Streptomyces exfoliatus UC5319. This cyclase generates the hydrocarbon precursor of the pentalenolactone family of antibiotics. The structures of pentalenene synthase and other terpenoid cyclases reveal predominantly nonpolar active sites typically lacking amino acid side chains capable of serving general base-general acid functions. What chemical species, then, enables the Brønsted acid-base chemistry required in the catalytic mechanisms of these enzymes? The most likely candidate for such general base-general acid chemistry is the co-product inorganic pyrophosphate. Here, we briefly review biological and nonbiological systems in which phosphate and its derivatives serve general base and general acid functions in catalysis. These examples highlight the fact that the Brønsted acid-base activities of phosphate derivatives are comparable to the Brønsted acid-base activities of amino acid side chains.

Effects of diet on titratable acid-base excretion in grasshoppers.

PubMed

Frazier, M R; Harrison, J F; Behmer, S T

2000-01-01

Despite the potential for diet to affect organismal acid-base status, especially in herbivores, little is known about the effects of diet on acid-base loading and excretion. We tested the effects of diet on acid-base loading and excretion in grasshoppers by (a) comparing the fecal acid-base content of 15 grasshopper species collected from the field and (b) comparing fecal acid-base excretion rates of Schistocerca americana grasshoppers fed vegetable diets that differed in their ashed and raw acid-base contents. The field experiments indicated that grass-feeding species excrete fairly neutral fecal pellets, while forb/mixed-feeding species vary widely in their fecal acid-base contents. In the laboratory experiment, acid-base excretion rates were positively correlated with dietary ashed base intake rates but were not correlated with the acid-base content of raw, unashed diet or feeding rate. These experiments suggest that some diets could strongly challenge the acid-base homeostasis of herbivores; in some grasshoppers, dietary acid-base loads could produce certainly lethal 1-unit changes in average body pH within 6 h if they were not excreted.

The Kidney and Acid-Base Regulation

ERIC Educational Resources Information Center

Koeppen, Bruce M.

2009-01-01

Since the topic of the role of the kidneys in the regulation of acid base balance was last reviewed from a teaching perspective (Koeppen BM. Renal regulation of acid-base balance. Adv Physiol Educ 20: 132-141, 1998), our understanding of the specific membrane transporters involved in H+, HCO , and NH transport, and especially how these…

Acid-base properties of 2-phenethyldithiocarbamoylacetic acid, an antitumor agent

NASA Astrophysics Data System (ADS)

Novozhilova, N. E.; Kutina, N. N.; Petukhova, O. A.; Kharitonov, Yu. Ya.

2013-07-01

The acid-base properties of the 2-phenethyldithiocarbamoylacetic acid (PET) substance belonging to the class of isothiocyanates and capable of inhibiting the development of tumors on many experimental models were studied. The acidity and hydrolysis constants of the PET substance in ethanol, acetone, aqueous ethanol, and aqueous acetone solutions were determined from the data of potentiometric (pH-metric) titration of ethanol and acetone solutions of PET with aqueous solidum hydroxide at room temperature.

Acid-base properties of humic and fulvic acids formed during composting.

PubMed

Plaza, César; Senesi, Nicola; Polo, Alfredo; Brunetti, Gennaro

2005-09-15

The soil acid-base buffering capacity and the biological availability, mobilization, and transport of macro- and micronutrients, toxic metal ions, and xenobiotic organic cations in soil are strongly influenced by the acid-base properties of humic substances, of which humic and fulvic acids are the major fractions. For these reasons, the proton binding behavior of the humic acid-like (HA) and fulvic acid-like (FA) fractions contained in a compost are believed to be instrumental in its successful performance in soil. In this work, the acid-base properties of the HAs and FAs isolated from a mixture of the sludge residue obtained from olive oil mill wastewater (OMW) evaporated in an open-air pond and tree cuttings (TC) at different stages of composting were investigated by a current potentiometric titration method and the nonideal competitive adsorption (NICA)-Donnan model. The NICA-Donnan model provided an excellent description of the acid-base titration data, and pointed out substantial differences in site density and proton-binding affinity between the HAs and FAs examined. With respect to FAs, HAs were characterized by a smaller content of carboxylic- and phenolic-type groups and their larger affinities for proton binding. Further, HAs featured a greater heterogeneity in carboxylic-type groups than FAs. The composting process increased the content and decreased the proton affinity of carboxylic- and phenolic-type groups of HAs and FAs, and increased the heterogeneity of phenolic-type groups of HAs. As a whole, these effects indicated that the composting process could produce HA and FA fractions with greater cation binding capacities. These results suggest that composting of organic materials improves their agronomic and environmental value by increasing their potential to retain and exchange macro- and micronutrients, and to reduce the bioavailability of organic and inorganic pollutants.

Determination of Anti-Adeno-Associated Virus Vector Neutralizing Antibody Titer with an In Vitro Reporter System

PubMed Central

Meliani, Amine; Leborgne, Christian; Triffault, Sabrina; Jeanson-Leh, Laurence; Veron, Philippe

2015-01-01

Abstract Adeno-associated virus (AAV) vectors are a platform of choice for in vivo gene transfer applications. However, neutralizing antibodies (NAb) to AAV can be found in humans and some animal species as a result of exposure to the wild-type virus, and high-titer NAb develop following AAV vector administration. In some conditions, anti-AAV NAb can block transduction with AAV vectors even when present at low titers, thus requiring prescreening before vector administration. Here we describe an improved in vitro, cell-based assay for the determination of NAb titer in serum or plasma samples. The assay is easy to setup and sensitive and, depending on the purpose, can be validated to support clinical development of gene therapy products based on AAV vectors. PMID:25819687

Renal acidification responses to respiratory acid-base disorders.

PubMed

Madias, Nicolaos E

2010-01-01

Respiratory acid-base disorders are those abnormalities in acid-base equilibrium that are expressed as primary changes in the arterial carbon dioxide tension (PaCO2). An increase in PaCO2 (hypercapnia) acidifies body fluids and initiates the acid-base disturbance known as respiratory acidosis. By contrast, a decrease in PaCO2 (hypocapnia) alkalinizes body fluids and initiates the acid-base disturbance known as respiratory alkalosis. The impact on systemic acidity of these primary changes in PaCO2 is ameliorated by secondary, directional changes in plasma [HCO3¯] that occur in 2 stages. Acutely, hypercapnia or hypocapnia yields relatively small changes in plasma [HCO3¯] that originate virtually exclusively from titration of the body's nonbicarbonate buffers. During sustained hypercapnia or hypocapnia, much larger changes in plasma [HCO3¯] occur that reflect adjustments in renal acidification mechanisms. Consequently, the deviation of systemic acidity from normal is smaller in the chronic forms of these disorders. Here we provide an overview of the renal acidification responses to respiratory acid-base disorders. We also identify gaps in knowledge that require further research.

Nucleic Acid-Based Nanodevices in Biological Imaging.

PubMed

Chakraborty, Kasturi; Veetil, Aneesh T; Jaffrey, Samie R; Krishnan, Yamuna

2016-06-02

The nanoscale engineering of nucleic acids has led to exciting molecular technologies for high-end biological imaging. The predictable base pairing, high programmability, and superior new chemical and biological methods used to access nucleic acids with diverse lengths and in high purity, coupled with computational tools for their design, have allowed the creation of a stunning diversity of nucleic acid-based nanodevices. Given their biological origin, such synthetic devices have a tremendous capacity to interface with the biological world, and this capacity lies at the heart of several nucleic acid-based technologies that are finding applications in biological systems. We discuss these diverse applications and emphasize the advantage, in terms of physicochemical properties, that the nucleic acid scaffold brings to these contexts. As our ability to engineer this versatile scaffold increases, its applications in structural, cellular, and organismal biology are clearly poised to massively expand.

Nanoparticle albumin-bound paclitaxel: a novel Cremphor-EL-free formulation of paclitaxel.

PubMed

Stinchcombe, Thomas E

2007-08-01

Standard formulation paclitaxel requires the use of solvents, such as Cremphor-EL, which contribute to some of the toxicities commonly associated with paclitaxel-based therapy. Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is a novel solvent-free formulation of paclitaxel. The formulation is prepared by high-pressure homogenization of paclitaxel in the presence of serum albumin into a nanoparticle colloidal suspension. The human albumin-stabilized paclitaxel particles have an average size of 130 nm. Nab-paclitaxel has several practical advantages over Cremphor-EL-paclitaxel, including a shorter infusion time (30 min) and no need for premedications for hypersensitivity reactions. The nab-paclitaxel formulation eliminates the impact of Cremphor-EL on paclitaxel pharmacokinetics and utilizes the endogenous albumin transport mechanisms to concentrate nab-paclitaxel within the tumor. A recent Phase III trial compared nab- and Cremphor-EL-paclitaxel in patients with metastatic breast cancer. Patients treated with nab-paclitaxel experienced a higher response, longer time to tumor progression and, in patients receiving second-line or greater therapy, a longer median survival. Patients treated with nab-paclitaxel had a significantly lower rate of severe neutropenia and a higher rate of sensory neuropathy. The preclinical and clinical data indicate that the nab-paclitaxel formulation has significant advantages over Cremphor-EL-paclitaxel.

Patterns of HIV/SIV Prevention and Control by Passive Antibody Immunization.

PubMed

Yamamoto, Hiroyuki; Matano, Tetsuro

2016-01-01

Neutralizing antibody (NAb) responses are promising immune effectors for control of human immunodeficiency virus (HIV) infection. Protective activity and mechanisms of immunodeficiency virus-specific NAbs have been increasingly scrutinized in animals infected with simian immunodeficiency virus (SIV), chimeric simian/human immunodeficiency virus (SHIV) and related viruses. Studies on such models have unraveled a previously underscored protective potential against in vivo immunodeficiency virus replication. Pre-challenge NAb titers feasibly provide sterile protection from SIV/SHIV infection by purging the earliest onset of viral replication and likely modulate innate immune cell responses. Sufficient sub-sterile NAb titers after established infection also confer dose-dependent reduction of viremia, and in certain earlier time frames augment adaptive immune cell responses and even provide rebound-free viral control. Here, we provide an overview of the obtained patterns of SIV/SHIV protection and viral control by various types of NAb passive immunizations and discuss how these notions may be extrapolated to NAb-based clinical control of HIV infection.

Seroprevalence of Neutralizing Antibodies against Human Adenovirus Type-5 and Chimpanzee Adenovirus Type-68 in Cancer Patients.

PubMed

Zhao, Hua; Xu, Can; Luo, Xiaoli; Wei, Feng; Wang, Ning; Shi, Huiying; Ren, Xiubao

2018-01-01

Since the preclinical results about chimpanzee adenovirus serotype-68 (AdC68)-based vaccine showed an encouraging results, it reminded us that AdC68 may be a suitable cancer vaccine vector. Previous study indicated that the seroprevalence of neutralizing antibodies (NAbs) against adenovirus was different between cancer patients and healthy volunteers. Knowledge regarding the prevalence rates of AdC68 NAbs for cancer patients is lacking. Therefore, assessing the preexistence of NAbs against AdC68 in cancer patients could provide useful insights for developing future AdC68-based cancer vaccines. In this study, 440 patients with different pathological types of tumors and 204 healthy adult volunteers were enrolled to evaluate the NAbs against AdC68 and human adenovirus serotype-5 (AdHu5). The seroprevalence of NAbs against AdC68 was much lower than that against AdHu5 in cancer subjects (43.64 vs. 67.05%, P  < 0.01). The seroprevalence rates of NAbs to AdC68 in the cancer subjects were statistically higher than those detected in the healthy adult volunteers (43.64 vs. 23.53%, P  = 0.000). The seroprevalence rates of AdC68 NAbs were much lower in lung, laryngeal, esophageal, and cervical cancer patients compared with oropharyngeal, colon, and rectal cancer patients. Furthermore, the seroprevalence rates of AdC68 NAbs were much lower in lung adenocarcinoma patients than in lung squamous cell carcinoma patients (35.00 vs. 70.00%, P  < 0.05). No significant difference in the AdC68 NAbs among patients with different clinical stages of cancer was detected. The percentage of NAbs against AdC68 was significantly lower than that against AdHu5 ( P  < 0.05) in stage-I, -II, and -III cancer patients. No significant difference between the percentage of NAbs against AdC68 and AdHu5 in the subjects with stage-IV cancer was detected. The study also demonstrated the distribution of AdHu5 and AdC68 NAb titers for the positive samples. It showed that very low NAb titers

Seroprevalence of Neutralizing Antibodies against Human Adenovirus Type-5 and Chimpanzee Adenovirus Type-68 in Cancer Patients

PubMed Central

Zhao, Hua; Xu, Can; Luo, Xiaoli; Wei, Feng; Wang, Ning; Shi, Huiying; Ren, Xiubao

2018-01-01

Since the preclinical results about chimpanzee adenovirus serotype-68 (AdC68)-based vaccine showed an encouraging results, it reminded us that AdC68 may be a suitable cancer vaccine vector. Previous study indicated that the seroprevalence of neutralizing antibodies (NAbs) against adenovirus was different between cancer patients and healthy volunteers. Knowledge regarding the prevalence rates of AdC68 NAbs for cancer patients is lacking. Therefore, assessing the preexistence of NAbs against AdC68 in cancer patients could provide useful insights for developing future AdC68-based cancer vaccines. In this study, 440 patients with different pathological types of tumors and 204 healthy adult volunteers were enrolled to evaluate the NAbs against AdC68 and human adenovirus serotype-5 (AdHu5). The seroprevalence of NAbs against AdC68 was much lower than that against AdHu5 in cancer subjects (43.64 vs. 67.05%, P < 0.01). The seroprevalence rates of NAbs to AdC68 in the cancer subjects were statistically higher than those detected in the healthy adult volunteers (43.64 vs. 23.53%, P = 0.000). The seroprevalence rates of AdC68 NAbs were much lower in lung, laryngeal, esophageal, and cervical cancer patients compared with oropharyngeal, colon, and rectal cancer patients. Furthermore, the seroprevalence rates of AdC68 NAbs were much lower in lung adenocarcinoma patients than in lung squamous cell carcinoma patients (35.00 vs. 70.00%, P < 0.05). No significant difference in the AdC68 NAbs among patients with different clinical stages of cancer was detected. The percentage of NAbs against AdC68 was significantly lower than that against AdHu5 (P < 0.05) in stage-I, -II, and -III cancer patients. No significant difference between the percentage of NAbs against AdC68 and AdHu5 in the subjects with stage-IV cancer was detected. The study also demonstrated the distribution of AdHu5 and AdC68 NAb titers for the positive samples. It showed that very low NAb titers against

Acid-base titrations using microfluidic paper-based analytical devices.

PubMed

Karita, Shingo; Kaneta, Takashi

2014-12-16

Rapid and simple acid-base titration was accomplished using a novel microfluidic paper-based analytical device (μPAD). The μPAD was fabricated by wax printing and consisted of ten reservoirs for reaction and detection. The reaction reservoirs contained various amounts of a primary standard substance, potassium hydrogen phthalate (KHPth), whereas a constant amount of phenolphthalein was added to all the detection reservoirs. A sample solution containing NaOH was dropped onto the center of the μPAD and was allowed to spread to the reaction reservoirs where the KHPth neutralized it. When the amount of NaOH exceeded that of the KHPth in the reaction reservoirs, unneutralized hydroxide ion penetrated the detection reservoirs, resulting in a color reaction from the phenolphthalein. Therefore, the number of the detection reservoirs with no color change determined the concentration of the NaOH in the sample solution. The titration was completed within 1 min by visually determining the end point, which required neither instrumentation nor software. The volumes of the KHPth and phenolphthalein solutions added to the corresponding reservoirs were optimized to obtain reproducible and accurate results for the concentration of NaOH. The μPADs determined the concentration of NaOH at orders of magnitude ranging from 0.01 to 1 M. An acid sample, HCl, was also determined using Na2CO3 as a primary standard substance instead of KHPth. Furthermore, the μPAD was applicable to the titrations of nitric acid, sulfuric acid, acetic acid, and ammonia solutions. The μPADs were stable for more than 1 month when stored in darkness at room temperature, although this was reduced to only 5 days under daylight conditions. The analysis of acidic hot spring water was also demonstrated in the field using the μPAD, and the results agreed well with those obtained by classic acid-base titration.

Structure-based Design of Cyclically Permuted HIV-1 gp120 Trimers That Elicit Neutralizing Antibodies*

PubMed Central

Kesavardhana, Sannula; Das, Raksha; Citron, Michael; Datta, Rohini; Ecto, Linda; Srilatha, Nonavinakere Seetharam; DiStefano, Daniel; Swoyer, Ryan; Joyce, Joseph G.; Dutta, Somnath; LaBranche, Celia C.; Montefiori, David C.; Flynn, Jessica A.; Varadarajan, Raghavan

2017-01-01

A major goal for HIV-1 vaccine development is an ability to elicit strong and durable broadly neutralizing antibody (bNAb) responses. The trimeric envelope glycoprotein (Env) spikes on HIV-1 are known to contain multiple epitopes that are susceptible to bNAbs isolated from infected individuals. Nonetheless, all trimeric and monomeric Env immunogens designed to date have failed to elicit such antibodies. We report the structure-guided design of HIV-1 cyclically permuted gp120 that forms homogeneous, stable trimers, and displays enhanced binding to multiple bNAbs, including VRC01, VRC03, VRC-PG04, PGT128, and the quaternary epitope-specific bNAbs PGT145 and PGDM1400. Constructs that were cyclically permuted in the V1 loop region and contained an N-terminal trimerization domain to stabilize V1V2-mediated quaternary interactions, showed the highest homogeneity and the best antigenic characteristics. In guinea pigs, a DNA prime-protein boost regimen with these new gp120 trimer immunogens elicited potent neutralizing antibody responses against highly sensitive Tier 1A isolates and weaker neutralizing antibody responses with an average titer of about 115 against a panel of heterologous Tier 2 isolates. A modest fraction of the Tier 2 virus neutralizing activity appeared to target the CD4 binding site on gp120. These results suggest that cyclically permuted HIV-1 gp120 trimers represent a viable platform in which further modifications may be made to eventually achieve protective bNAb responses. PMID:27879316

Chem I Supplement: Emphasis on Acids and Bases

ERIC Educational Resources Information Center

Journal of Chemical Education Staff

1977-01-01

Provides supplementary notes on acids and bases suitable for secondary school chemistry instruction, including acidity in solid and natural waters, acidity balance in body chemistry, acid and basic foods, pH values of common fluids, examples of drugs, and commercial preparation of nitric acid. (SL)

Prediction of HIV-1 sensitivity to broadly neutralizing antibodies shows a trend towards resistance over time.

PubMed

Hake, Anna; Pfeifer, Nico

2017-10-01

Treatment with broadly neutralizing antibodies (bNAbs) has proven effective against HIV-1 infections in humanized mice, non-human primates, and humans. Due to the high mutation rate of HIV-1, resistance testing of the patient's viral strains to the bNAbs is still inevitable. So far, bNAb resistance can only be tested in expensive and time-consuming neutralization experiments. Here, we introduce well-performing computational models that predict the neutralization response of HIV-1 to bNAbs given only the envelope sequence of the virus. Using non-linear support vector machines based on a string kernel, the models learnt even the important binding sites of bNAbs with more complex epitopes, i.e., the CD4 binding site targeting bNAbs, proving thereby the biological relevance of the models. To increase the interpretability of the models, we additionally provide a new kind of motif logo for each query sequence, visualizing those residues of the test sequence that influenced the prediction outcome the most. Moreover, we predicted the neutralization sensitivity of around 34,000 HIV-1 samples from different time points to a broad range of bNAbs, enabling the first analysis of HIV resistance to bNAbs on a global scale. The analysis showed for many of the bNAbs a trend towards antibody resistance over time, which had previously only been discovered for a small non-representative subset of the global HIV-1 population.

Prediction of HIV-1 sensitivity to broadly neutralizing antibodies shows a trend towards resistance over time

PubMed Central

2017-01-01

Treatment with broadly neutralizing antibodies (bNAbs) has proven effective against HIV-1 infections in humanized mice, non-human primates, and humans. Due to the high mutation rate of HIV-1, resistance testing of the patient’s viral strains to the bNAbs is still inevitable. So far, bNAb resistance can only be tested in expensive and time-consuming neutralization experiments. Here, we introduce well-performing computational models that predict the neutralization response of HIV-1 to bNAbs given only the envelope sequence of the virus. Using non-linear support vector machines based on a string kernel, the models learnt even the important binding sites of bNAbs with more complex epitopes, i.e., the CD4 binding site targeting bNAbs, proving thereby the biological relevance of the models. To increase the interpretability of the models, we additionally provide a new kind of motif logo for each query sequence, visualizing those residues of the test sequence that influenced the prediction outcome the most. Moreover, we predicted the neutralization sensitivity of around 34,000 HIV-1 samples from different time points to a broad range of bNAbs, enabling the first analysis of HIV resistance to bNAbs on a global scale. The analysis showed for many of the bNAbs a trend towards antibody resistance over time, which had previously only been discovered for a small non-representative subset of the global HIV-1 population. PMID:29065122

Evaluation of a computer-based approach to teaching acid/base physiology.

PubMed

Rawson, Richard E; Quinlan, Kathleen M

2002-12-01

Because acid/base physiology is a difficult subject for most medical and veterinary students, the first author designed a software program, Acid/Base Primer, that would help students with this topic. The Acid/Base Primer was designed and evaluated within a conceptual framework of basic educational principles. Seventy-five first-year veterinary students (of 81; 93% response rate) participated in this study. Students took both a pre- and posttest of content understanding. After completing the Acid/Base Primer in pairs, each student filled out a survey evaluating the features of the program and describing his/her use and experience of it. Four pairs of students participated in interviews that elaborated on the surveys. Scores improved from 53 +/- 2% on the pretest to 74 +/- 1% on an immediate posttest. On surveys and in interviews, students reported that the program helped them construct their own understanding of acid/base physiology and prompted discussions in pairs of students when individual understandings differed. The case-based format provided anchors and a high degree of relevance. Repetition of concepts helped students develop a more complex network of understanding. Questions in the program served to scaffold the learning process by providing direction, accentuating the relevant features of the cases, and provoking discussion. Guidelines for software development were generated on the basis of the findings and relevant educational literature.

p21ras independent down-regulation of ras-induced increases in natural antibody binding during tumor progression.

PubMed

Tough, D F; Feng, X; Chow, D A

1995-01-01

Selective outgrowth of v-H-ras-infected 10T1/2 cells based on the cointroduction of a gene for resistance to geneticin (G418), yielded cells which exhibited an increased capacity to bind polyclonal serum natural antibody (NAb). This demonstrated an NAb-susceptible phase of tumor development which would be a basic requirement for NAb-mediated surveillance of tumors. The ras-oncogene dependence of the high-NAb-binding phenotype provided a model for assessing NAb resistance against ras transformants in vivo and for a comparative analysis of phenotypic and genetic alterations contributing to the progression of ras transformants. Variants were developed through in vitro and in vivo models of tumor progression. T24-H-ras and v-H-ras transformants were isolated in vitro through more rigorous growth conditions, focus formation in the presence of untransformed cells with no selecting drug. These clones expressed p21ras but exhibited little or no increase in NAb binding. Variants recovered following growth from intravenous or threshold subcutaneous (s.c.) inocula of high-NAb-binding ras transformants in syngeneic C3H/HeN mice exhibited decreases in NAb binding but no uniform change in p21ras. Concurring inverse correlations between NAb binding and s.c. tumorigenicity were exhibited by the T24-H-ras transformant clones, the ras transformants grown in vivo, and the v-H-ras-transformed clones isolated in the presence versus the absence of untransformed cells. This consistent inverse correlation, together with the reduced NAb binding of the ras transformants grown in vivo, provides strong evidence that NAb participates in the defense against ras-transformed cells in vivo. The lack of any direct correlation between p21ras expression and the reduction in NAb binding or the increase in tumorigenicity of cells generated through progression in vivo suggested the regulatory action of additional genes. Hybridization studies between high- and low-NAb-binding clones implicated the

The acid-base resistant zone in three dentin bonding systems.

PubMed

Inoue, Go; Nikaido, Toru; Foxton, Richard M; Tagami, Junji

2009-11-01

An acid-base resistant zone has been found to exist after acid-base challenge adjacent to the hybrid layer using SEM. The aim of this study was to examine the acid-base resistant zone using three different bonding systems. Dentin disks were applied with three different bonding systems, and then a resin composite was light-cured to make dentin disk sandwiches. After acid-base challenge, the polished surfaces were observed using SEM. For both one- and two-step self-etching primer systems, an acid-base resistant zone was clearly observed adjacent to the hybrid layer - but with differing appearances. For the wet bonding system, the presence of an acid-base resistant zone was unclear. This was because the self-etching primer systems etched the dentin surface mildly, such that the remaining mineral phase of dentin and the bonding agent yielded clear acid-base resistant zones. In conclusion, the acid-base resistant zone was clearly observed when self-etching primer systems were used, but not so for the wet bonding system.

General Base-General Acid Catalysis by Terpenoid Cyclases§

PubMed Central

Pemberton, Travis A.; Christianson, David W.

2016-01-01

Terpenoid cyclases catalyze the most complex reactions in biology, in that more than half of the substrate carbon atoms often undergo changes in bonding during the course of a multistep cyclization cascade that proceeds through multiple carbocation intermediates. Many cyclization mechanisms require stereospecific deprotonation and reprotonation steps, and most cyclization cascades are terminated by deprotonation to yield an olefin product. The first bacterial terpenoid cyclase to yield a crystal structure was pentalenene synthase from Streptomyces exfoliatus UC5319. This cyclase generates the hydrocarbon precursor of the pentalenolactone family of antibiotics. The structures of pentalenene synthase and other terpenoid cyclases reveal predominantly nonpolar active sites typically lacking amino acid side chains capable of serving general base-general acid functions. What chemical species, then, enables the Brønsted acid-base chemistry required in the catalytic mechanisms of these enzymes? The most likely candidate for such general base-general acid chemistry is the co-product inorganic pyrophosphate. Here, we briefly review biological and nonbiological systems in which phosphate and its derivatives serve general base and general acid functions in catalysis. These examples highlight the fact that the Brønsted acid-base activities of phosphate derivatives are comparable to the Brønsted acid-base activities of amino acid side chains. PMID:27072285

Ammonia Transporters and Their Role in Acid-Base Balance

PubMed Central

2017-01-01

Acid-base homeostasis is critical to maintenance of normal health. Renal ammonia excretion is the quantitatively predominant component of renal net acid excretion, both under basal conditions and in response to acid-base disturbances. Although titratable acid excretion also contributes to renal net acid excretion, the quantitative contribution of titratable acid excretion is less than that of ammonia under basal conditions and is only a minor component of the adaptive response to acid-base disturbances. In contrast to other urinary solutes, ammonia is produced in the kidney and then is selectively transported either into the urine or the renal vein. The proportion of ammonia that the kidney produces that is excreted in the urine varies dramatically in response to physiological stimuli, and only urinary ammonia excretion contributes to acid-base homeostasis. As a result, selective and regulated renal ammonia transport by renal epithelial cells is central to acid-base homeostasis. Both molecular forms of ammonia, NH3 and NH4+, are transported by specific proteins, and regulation of these transport processes determines the eventual fate of the ammonia produced. In this review, we discuss these issues, and then discuss in detail the specific proteins involved in renal epithelial cell ammonia transport. PMID:28151423

Assessing College Students' Understanding of Acid Base Chemistry Concepts

ERIC Educational Resources Information Center

Wan, Yanjun Jean

2014-01-01

Typically most college curricula include three acid base models: Arrhenius', Bronsted-Lowry's, and Lewis'. Although Lewis' acid base model is generally thought to be the most sophisticated among these three models, and can be further applied in reaction mechanisms, most general chemistry curricula either do not include Lewis' acid base model, or…

Preparation and Optimization of Amorphous Ursodeoxycholic Acid Nano-suspensions by Nanoprecipitation based on Acid-base Neutralization for Enhanced Dissolution.

PubMed

Xie, Yike; Chen, Zhongjian; Su, Rui; Li, Ye; Qi, Jianping; Wu, Wei; Lu, Yi

2017-01-01

Ursodeoxycholic acid, usually used to dissolve cholesterol gallstones in clinic, is a typical hydrophobic drug with poor oral bioavailability due to dissolution rate-limited performance. The objective of this study was to increase the dissolution of ursodeoxycholic acid by amorphous nanosuspensions. Nanoprecipitation based on acid-base neutralization was used to prepare the nanosuspensions with central composite design to optimize the formula. The nanosuspensions were characterized by particle size, morphology, crystallology and dissolution. The ursodeoxycholic acid nanosuspensions showed mean particle size around 380 nm with polydispersion index value about 0.25. Scanning electron microscope observed high coverage of HPMC-E50 onto the surface of the nanosuspensions. Differential scanning calorimetry and powder X-ray diffractometry revealed amorphous structure of the ursodeoxycholic acid nanosuspensions. A significant increase of dissolution in acidic media was achieved by the amorphous nanosuspensions compared with the physical mixture. It can be predicted that the amorphous nanosuspensions show great potential in improving the oral bioavailability of ursodeoxycholic acid. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

An approach to complex acid-base problems

PubMed Central

Herd, Anthony M.

2005-01-01

OBJECTIVE To review rules and formulas for solving even the most complex acid-base problems. SOURCES OF INFORMATION MEDLINE was searched from January 1966 to December 2003. The search was limited to English-language review articles involving human subjects. Nine relevant review papers were found and provide the background. As this information is well established and widely accepted, it is not judged for strength of evidence, as is standard practice. MAIN MESSAGE An understanding of the body’s responses to acidemia or alkalemia can be gained through a set of four rules and two formulas that can be used to interpret almost any acid-base problems. Physicians should, however, remember the “golden rule” of acid-base interpretation: always look at a patient’s clinical condition. CONCLUSION Physicians practising in acute care settings commonly encounter acid-base disturbances. While some of these are relatively simple and easy to interpret, some are more complex. Even complex cases can be resolved using the four rules and two formulas. PMID:15751566

Nucleic acid duplexes incorporating a dissociable covalent base pair

NASA Technical Reports Server (NTRS)

Gao, K.; Orgel, L. E.; Bada, J. L. (Principal Investigator)

1999-01-01

We have used molecular modeling techniques to design a dissociable covalently bonded base pair that can replace a Watson-Crick base pair in a nucleic acid with minimal distortion of the structure of the double helix. We introduced this base pair into a potential precursor of a nucleic acid double helix by chemical synthesis and have demonstrated efficient nonenzymatic template-directed ligation of the free hydroxyl groups of the base pair with appropriate short oligonucleotides. The nonenzymatic ligation reactions, which are characteristic of base paired nucleic acid structures, are abolished when the covalent base pair is reduced and becomes noncoplanar. This suggests that the covalent base pair linking the two strands in the duplex is compatible with a minimally distorted nucleic acid double-helical structure.

Nucleic acid duplexes incorporating a dissociable covalent base pair

PubMed Central

Gao, Kui; Orgel, Leslie E.

1999-01-01

We have used molecular modeling techniques to design a dissociable covalently bonded base pair that can replace a Watson-Crick base pair in a nucleic acid with minimal distortion of the structure of the double helix. We introduced this base pair into a potential precursor of a nucleic acid double helix by chemical synthesis and have demonstrated efficient nonenzymatic template-directed ligation of the free hydroxyl groups of the base pair with appropriate short oligonucleotides. The nonenzymatic ligation reactions, which are characteristic of base paired nucleic acid structures, are abolished when the covalent base pair is reduced and becomes noncoplanar. This suggests that the covalent base pair linking the two strands in the duplex is compatible with a minimally distorted nucleic acid double-helical structure. PMID:10611299

Using Willie's Acid-Base Box for Blood Gas Analysis

ERIC Educational Resources Information Center

Dietz, John R.

2011-01-01

In this article, the author describes a method developed by Dr. William T. Lipscomb for teaching blood gas analysis of acid-base status and provides three examples using Willie's acid-base box. Willie's acid-base box is constructed using three of the parameters of standard arterial blood gas analysis: (1) pH; (2) bicarbonate; and (3) CO[subscript…

Students' Alternate Conceptions on Acids and Bases

ERIC Educational Resources Information Center

Pan, Hanqing; Henriques, Laura

2015-01-01

Knowing what students bring to the classroom can and should influence how we teach them. This study is a review of the literature associated with secondary and postsecondary students' ideas about acids and bases. It was found that there are six types of alternate ideas about acids and bases that students hold. These are: macroscopic properties of…

Hydroxamic acids as weak base indicators: protonation in strong acid media.

PubMed

García, B; Ibeas, S; Hoyuelos, F J; Leal, J M; Secco, F; Venturini, M

2001-11-30

The protonation equilibria of N-phenylbenzohydroxamic, benzohydroxamic, salicylhydroxamic, and N-p-tolylcinnamohydroxamic acids have been studied at 25 degrees C in concentrated sulfuric, hydrochloric, and perchloric acid media; the UV-vis spectral measurements were analyzed using the Hammett equation and the Bunnett-Olsen and excess acidity methods. The medium effects observed in the UV spectral curves were corrected with the Cox-Yates and vector analysis methods. The H(A) acidity function based on benzamides provided the best results. The range of variation of the solvation coefficient m is similar to that of amides, this indicating similar solvation requirements for amides and hydroxamic acids. For the same substrate, the observed variations of pK(BH)(+) with the mineral acid used was justified by formation of solvent-separated ion pairs; for the same mineral acid, the observed changes in pK(BH)(+) can be explained by the solvation of BH(+). The change of the pK(BH)(+) values was in reasonably good agreement with the sequence of the catalytic efficiency of the mineral acids used, HCl > H(2)SO(4) > HClO(4).

Use of flow cytometry, fluorescence microscopy, and PCR-based techniques to assess intraspecific and interspecific matings of Armillaria species

Treesearch

Mee-Sook Kim; Ned B. Klopfenstein; Geral I. McDonald; Kathiravetpillai Arumuganathan

2001-01-01

For assessments of intraspecific mating using flow cytometry and fluorescence microscopy, two compatible basidiospore-derived isolates were selected from each of four parental basidiomata of North American Biological Species (NABS) X. The nuclear status in NABS X varied with basidiospore-derived isolates. Nuclei within basidiospore-derived isolates existed as haploids...

Structure-based conformational preferences of amino acids

PubMed Central

Koehl, Patrice; Levitt, Michael

1999-01-01

Proteins can be very tolerant to amino acid substitution, even within their core. Understanding the factors responsible for this behavior is of critical importance for protein engineering and design. Mutations in proteins have been quantified in terms of the changes in stability they induce. For example, guest residues in specific secondary structures have been used as probes of conformational preferences of amino acids, yielding propensity scales. Predicting these amino acid propensities would be a good test of any new potential energy functions used to mimic protein stability. We have recently developed a protein design procedure that optimizes whole sequences for a given target conformation based on the knowledge of the template backbone and on a semiempirical potential energy function. This energy function is purely physical, including steric interactions based on a Lennard-Jones potential, electrostatics based on a Coulomb potential, and hydrophobicity in the form of an environment free energy based on accessible surface area and interatomic contact areas. Sequences designed by this procedure for 10 different proteins were analyzed to extract conformational preferences for amino acids. The resulting structure-based propensity scales show significant agreements with experimental propensity scale values, both for α-helices and β-sheets. These results indicate that amino acid conformational preferences are a natural consequence of the potential energy we use. This confirms the accuracy of our potential and indicates that such preferences should not be added as a design criterion. PMID:10535955

Solid-state acid-base interactions in complexes of heterocyclic bases with dicarboxylic acids: crystallography, hydrogen bond analysis, and 15N NMR spectroscopy.

PubMed

Li, Z Jane; Abramov, Yuriy; Bordner, Jon; Leonard, Jason; Medek, Ales; Trask, Andrew V

2006-06-28

A cancer candidate, compound 1, is a weak base with two heterocyclic basic nitrogens and five hydrogen-bonding functional groups, and is sparingly soluble in water rendering it unsuitable for pharmaceutical development. The crystalline acid-base pairs of 1, collectively termed solid acid-base complexes, provide significant increases in the solubility and bioavailability compared to the free base, 1. Three dicarboxylic acid-base complexes, sesquisuccinate 2, dimalonate 3, and dimaleate 4, show the most favorable physicochemical profiles and are studied in greater detail. The structural analyses of the three complexes using crystal structure and solid-state NMR reveal that the proton-transfer behavior in these organic acid-base complexes vary successively correlating with Delta pKa. As a result, 2 is a neutral complex, 3 is a mixed ionic and zwitterionic complex and 4 is an ionic salt. The addition of the acidic components leads to maximized hydrogen bond interactions forming extended three-dimensional networks. Although structurally similar, the packing arrangements of the three complexes are considerably different due to the presence of multiple functional groups and the flexible backbone of 1. The findings in this study provide insight into the structural characteristics of complexes involving heterocyclic bases and carboxylic acids, and demonstrate that X-ray crystallography and 15N solid-state NMR are truly complementary in elucidating hydrogen bonding interactions and the degree of proton transfer of these complexes.

Synthesis and characterization of boric acid mediated metal-organic frameworks based on trimesic acid and terephthalic acid

NASA Astrophysics Data System (ADS)

Ozer, Demet; Köse, Dursun A.; Şahin, Onur; Oztas, Nursen Altuntas

2017-08-01

The new metal-organic framework materials based on boric acid reported herein. Sodium and boron containing metal-organic frameworks were synthesized by one-pot self-assembly reaction in the presence of trimesic acid and terephthalic acid in water/ethanol solution. Boric acid is a relatively cheap boron source and boric acid mediated metal-organic framework prepared mild conditions compared to the other boron source based metal-organic framework. The synthesized compounds were characterized by FT-IR, p-XRD, TGA/DTA, elemental analysis, 13C-MAS NMR, 11B-NMR and single crystal measurements. The molecular formulas of compounds were estimated as C18H33B2Na5O28 and C8H24B2Na2O17 according to the structural analysis. The obtained complexes were thermally stable. Surface properties of inorganic polymer complexes were investigated by BET analyses and hydrogen storage properties of compound were also calculated.

Boronic acid-tethered amphiphilic hyaluronic acid derivative-based nanoassemblies for tumor targeting and penetration.

PubMed

Jeong, Jae Young; Hong, Eun-Hye; Lee, Song Yi; Lee, Jae-Young; Song, Jae-Hyoung; Ko, Seung-Hak; Shim, Jae-Seong; Choe, Sunghwa; Kim, Dae-Duk; Ko, Hyun-Jeong; Cho, Hyun-Jong

2017-04-15

(3-Aminomethylphenyl)boronic acid (AMPB)-installed hyaluronic acid-ceramide (HACE)-based nanoparticles (NPs), including manassantin B (MB), were fabricated for tumor-targeted delivery. The amine group of AMPB was conjugated to the carboxylic acid group of hyaluronic acid (HA) via amide bond formation, and synthesis was confirmed by spectroscopic methods. HACE-AMPB/MB NPs with a 239-nm mean diameter, narrow size distribution, negative zeta potential, and >90% drug encapsulation efficiency were fabricated. Exposed AMPB in the outer surface of HACE-AMPB NPs (in the aqueous environment) may react with sialic acid of cancer cells. The improved cellular accumulation efficiency, in vitro antitumor efficacy, and tumor penetration efficiency of HACE-AMPB/MB NPs, compared with HACE/MB NPs, in MDA-MB-231 cells (CD44 receptor-positive human breast adenocarcinoma cells) may be based on the CD44 receptor-mediated endocytosis and phenylboronic acid-sialic acid interaction. Enhanced in vivo tumor targetability, infiltration efficiency, and antitumor efficacies of HACE-AMPB NPs, compared with HACE NPs, were observed in a MDA-MB-231 tumor-xenografted mouse model. In addition to passive tumor targeting (based on an enhanced permeability and retention effect) and active tumor targeting (interaction between HA and CD44 receptor), the phenylboronic acid-sialic acid interaction can play important roles in augmented tumor targeting and penetration of HACE-AMPB NPs. STATEMENT OF SIGNIFICANCE: (3-Aminomethylphenyl)boronic acid (AMPB)-tethered hyaluronic acid-ceramide (HACE)-based nanoparticles (NPs), including manassantin B (MB), were fabricated and their tumor targeting and penetration efficiencies were assessed in MDA-MB-231 (CD44 receptor-positive human adenocarcinoma) tumor models. MB, which exhibited antitumor efficacies via the inhibition of angiogenesis and hypoxia inducible factor (HIF)-1, was entrapped in HACE-AMPB NPs in this study. Phenylboronic acid located in the outer surface

Applications of synchrotron-based spectroscopic techniques in studying nucleic acids and nucleic acid-functionalized nanomaterials

PubMed Central

Wu, Peiwen; Yu, Yang; McGhee, Claire E.; Tan, Li Huey

2014-01-01

In this review, we summarize recent progresses in the application of synchrotron-based spectroscopic techniques for nucleic acid research that takes advantage of high-flux and high-brilliance electromagnetic radiation from synchrotron sources. The first section of the review focuses on the characterization of the structure and folding processes of nucleic acids using different types of synchrotron-based spectroscopies, such as X-ray absorption spectroscopy, X-ray emission spectroscopy, X-ray photoelectron spectroscopy, synchrotron radiation circular dichroism, X-ray footprinting and small-angle X-ray scattering. In the second section, the characterization of nucleic acid-based nanostructures, nucleic acid-functionalized nanomaterials and nucleic acid-lipid interactions using these spectroscopic techniques is summarized. Insights gained from these studies are described and future directions of this field are also discussed. PMID:25205057

Applications of synchrotron-based spectroscopic techniques in studying nucleic acids and nucleic acid-functionalized nanomaterials

DOE PAGES

Wu, Peiwen; Yu, Yang; McGhee, Claire E.; ...

2014-09-10

In this paper, we summarize recent progress in the application of synchrotron-based spectroscopic techniques for nucleic acid research that takes advantage of high-flux and high-brilliance electromagnetic radiation from synchrotron sources. The first section of the review focuses on the characterization of the structure and folding processes of nucleic acids using different types of synchrotron-based spectroscopies, such as X-ray absorption spectroscopy, X-ray emission spectroscopy, X-ray photoelectron spectroscopy, synchrotron radiation circular dichroism, X-ray footprinting and small-angle X-ray scattering. In the second section, the characterization of nucleic acid-based nanostructures, nucleic acid-functionalized nanomaterials and nucleic acid-lipid interactions using these spectroscopic techniques is summarized. Insightsmore » gained from these studies are described and future directions of this field are also discussed.« less

Comparison of homologous and heterologous prime-boost vaccine approaches using Modified Vaccinia Ankara and soluble protein to induce neutralizing antibodies by the human cytomegalovirus pentamer complex in mice.

PubMed

Chiuppesi, Flavia; Wussow, Felix; Scharf, Louise; Contreras, Heidi; Gao, Han; Meng, Zhuo; Nguyen, Jenny; Barry, Peter A; Bjorkman, Pamela J; Diamond, Don J

2017-01-01

Since neutralizing antibodies (NAb) targeting the human cytomegalovirus (HCMV) pentamer complex (PC) potently block HCMV host cell entry, anti-PC NAb induction is thought to be important for a vaccine formulation to prevent HCMV infection. By developing a vaccine strategy based on soluble PC protein and using a previously generated Modified Vaccinia Ankara vector co-expressing all five PC subunits (MVA-PC), we compared HCMV NAb induction by homologous immunization using prime-boost vaccine regimen employing only PC protein or MVA-PC and heterologous immunization using prime-boost combinations of PC protein and MVA-PC. Utilizing a recently isolated anti-PC NAb, we produced highly pure soluble PC protein that displayed conformational and linear neutralizing epitopes, interfered with HCMV entry, and was recognized by antibodies induced by HCMV during natural infection. Mice vaccinated by different immunization routes with the purified PC protein in combination with a clinically approved adjuvant formulation elicited high-titer and durable HCMV NAb. While MVA-PC and soluble PC protein either alone or in combination elicited robust HCMV NAb, significantly different potencies of these vaccine approaches were observed in dependence on immunization schedule. Using only two immunizations, vaccination with MVA-PC alone or prime-boost combinations of MVA-PC and PC protein was significantly more effective in stimulating HCMV NAb than immunization with PC protein alone. In contrast, with three immunizations, NAb induced by soluble PC protein either alone or combined with two boosts of MVA-PC increased to levels that exceeded NAb titer stimulated by MVA-PC alone. These results provide insights into the potency of soluble protein and MVA to elicit NAb by the HCMV PC via homologous and heterologous prime-boost immunization, which may contribute to develop clinically deployable vaccine strategies to prevent HCMV infection.

Improved anticancer effects of albumin-bound paclitaxel nanoparticle via augmentation of EPR effect and albumin-protein interactions using S-nitrosated human serum albumin dimer.

PubMed

Kinoshita, Ryo; Ishima, Yu; Chuang, Victor T G; Nakamura, Hideaki; Fang, Jun; Watanabe, Hiroshi; Shimizu, Taro; Okuhira, Keiichiro; Ishida, Tatsuhiro; Maeda, Hiroshi; Otagiri, Masaki; Maruyama, Toru

2017-09-01

In the latest trend of anticancer chemotherapy research, there were many macromolecular anticancer drugs developed based on enhanced permeability and retention (EPR) effect, such as albumin bound paclitaxel nanoparticle (nab- PTX, also called Abraxane ® ). However, cancers with low vascular permeability posed a challenge for these EPR based therapeutic systems. Augmenting the intrinsic EPR effect with an intrinsic vascular modulator such as nitric oxide (NO) could be a promising strategy. S-nitrosated human serum albumin dimer (SNO-HSA Dimer) shown promising activity previously was evaluated for the synergistic effect when used as a pretreatment agent in nab-PTX therapy against various tumor models. In the high vascular permeability C26 murine colon cancer subcutaneous inoculation model, SNO-HSA Dimer enhanced tumor selectivity of nab-PTX, and attenuated myelosuppression. SNO-HSA Dimer also augmented the tumor growth inhibition of nab-PTX in low vascular permeability B16 murine melanoma subcutaneous inoculation model. Furthermore, nab-PTX therapy combined with SNO-HSA Dimer showed higher antitumor activity and improved survival rate of SUIT2 human pancreatic cancer orthotopic model. In conclusion, SNO-HSA Dimer could enhance the therapeutic effect of nab-PTX even in low vascular permeability or intractable pancreatic cancers. The possible underlying mechanisms of action of SNO-HSA Dimer were discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Acid-base chemistry and aluminum transport in an acidic watershed and pond in New Hampshire

Treesearch

Scott W. Bailey; Charles T. Driscoll; James W. Hornbeck

1995-01-01

Cone Pond is one of the few acidic, clear-water ponds in the White Mountains of New Hampshire, a region dominated by high inputs of strong acids from atmospheric deposition and low base content of bedrock. Monitoring was conducted for 13 months to compare and contrast the acid-base chemistry of the terrestrial and aquatic portions of the watershed. Variations in Al...

Adenovirus-Vectored Broadly Neutralizing Antibodies Directed Against gp120 Prevent Human Immunodeficiency Virus Type 1 Acquisition in Humanized Mice.

PubMed

Liu, Shan; Jackson, Andrew; Beloor, Jagadish; Kumar, Priti; Sutton, Richard E

2015-09-01

Despite nearly three decades of research, a safe and effective vaccine against human immunodeficiency virus type 1 (HIV-1) has yet to be achieved. More recently, the discovery of highly potent anti-gp160 broadly neutralizing antibodies (bNAbs) has garnered renewed interest in using antibody-based prophylactic and therapeutic approaches. Here, we encoded bNAbs in first-generation adenoviral (ADV) vectors, which have the distinctive features of a large coding capacity and ease of propagation. A single intramuscular injection of ADV-vectorized bNAbs in humanized mice generated high serum levels of bNAbs that provided protection against multiple repeated challenges with a high dose of HIV-1, prevented depletion of peripheral CD4(+) T cells, and reduced plasma viral loads to below detection limits. Our results suggest that ADV vectors may be a viable option for the prophylactic and perhaps therapeutic use of bNAbs in humans.

A Closer Look at Acid-Base Olfactory Titrations

ERIC Educational Resources Information Center

Neppel, Kerry; Oliver-Hoyo, Maria T.; Queen, Connie; Reed, Nicole

2005-01-01

Olfactory titrations using raw onions and eugenol as acid-base indicators are reported. An in-depth investigation on olfactory titrations is presented to include requirements for potential olfactory indicators and protocols for using garlic, onions, and vanillin as acid-base olfactory indicators are tested.

[Nutrition, acid-base metabolism, cation-anion difference and total base balance in humans].

PubMed

Mioni, R; Sala, P; Mioni, G

2008-01-01

The relationship between dietary intake and acid-base metabolism has been investigated in the past by means of the inorganic cation-anion difference (C(+)(nm)-A(-)(nm)) method based on dietary ash-acidity titration after the oxidative combustion of food samples. Besides the inorganic components of TA (A(-)(nm)-C(+)(nm)), which are under renal control, there are also metabolizable components (A(-)(nm)-C(+)(nm)) of TA, which are under the control of the intermediate metabolism. The whole body base balance, NBb(W), is obtained only by the application of C(+)(nm)-A(-)(nm) to food, feces and urine, while the metabolizable component (A(-)(nm)-C(+)(nm)) is disregarded. A novel method has been subsequently suggested to calculate the net balance of fixed acid, made up by the difference between the input of net endogenous acid production: NEAP = SO(4)(2-)+A(-)(m)-(C(+)(nm)-A(-)(nm)), and the output of net acid excretion: NAE = TA + NH(4)(+) - HCO(3)(-). This approach has been criticized because 1) it includes metabolizable acids, whose production cannot be measured independently; 2) the specific control of metabolizable acid and base has been incorrectly attributed to the kidney; 3) the inclusion of A-m in the balance input generates an acid overload; 4) the object of measurement in making up a balance has to be the same, a condition not fulfilled as NEAP is different from NAE. Lastly, by rearranging the net balance of the acid equation, the balance of nonmetabolizable acid equation is obtained. Therefore, any discrepancy between these two equations is due to the inaccuracy in the urine measurement of metabolizable cations and/or anions.

Thai Grade 11 students' alternative conceptions for acid-base chemistry

NASA Astrophysics Data System (ADS)

Artdej, Romklao; Ratanaroutai, Thasaneeya; Coll, Richard Kevin; Thongpanchang, Tienthong

2010-07-01

This study involved the development of a two-tier diagnostic instrument to assess Thai high school students' understanding of acid-base chemistry. The acid-base diagnostic test (ABDT) comprising 18 items was administered to 55 Grade 11 students in a science and mathematics programme during the second semester of the 2008 academic year. Analysis of students' responses from this study followed the methodology outlined by Çalik and Ayas. The research findings suggest that the ABDT, the multiple choice diagnostic instrument, enables researchers and teachers to classify students' understanding at different levels. Most students exhibited alternative conceptions for several concepts: acid-base theory, dissociation of strong acids or bases, and dissociation of weak acids/bases. Interestingly, one of the concepts that students appeared to find most difficult, and for which they exhibited the most alternative conceptions, was acid-base theory. Some alternative conceptions revealed in this study differ from earlier reports, such as the concept of electrolyte and non-electrolyte solutions as well as the concentration changes of H3O+and OH- in water. These research findings present valuable information for facilitating better understanding of acid-base chemistry by providing insight into the preventable and correctable alternative conceptions exhibited by students.

Acid-base homeostasis in the human system

NASA Technical Reports Server (NTRS)

White, R. J.

1974-01-01

Acid-base regulation is a cooperative phenomena in vivo with body fluids, extracellular and intracellular buffers, lungs, and kidneys all playing important roles. The present account is much too brief to be considered a review of present knowledge of these regulatory systems, and should be viewed, instead, as a guide to the elements necessary to construct a simple model of the mutual interactions of the acid-base regulatory systems of the body.

An Acid-Base Chemistry Example: Conversion of Nicotine

NASA Astrophysics Data System (ADS)

Summerfield, John H.

1999-10-01

The current government interest in nicotine conversion by cigarette companies provides an example of acid-base chemistry that can be explained to students in the second semester of general chemistry. In particular, the conversion by ammonia of the +1 form of nicotine to the easier-to-assimilate free-base form illustrates the effect of pH on acid-base equilibrium. The part played by ammonia in tobacco smoke is analogous to what takes place when cocaine is "free-based".

Controlling on-demand gastric acidity in obese subjects: a randomized, controlled trial comparing a single dose of 20 mg rabeprazole and 20 mg omeprazole.

PubMed

Belhocine, Kafia; Vavasseur, Fabienne; Volteau, Christelle; Flet, Laurent; Touchefeu, Yann; Bruley des Varannes, Stanislas

2014-07-15

Obesity is associated with a risk of gastroesophageal reflux disease. The pharmacodynamic efficacy of proton pump inhibitors has not been specifically evaluated in obese subjects. The aim of this study was to compare the antisecretory response to a single oral dose of 20 mg rabeprazole, 20 mg omeprazole and placebo in obese subjects. Gastric pH was monitored for 24 hours on three separate occasions in eighteen H. pylori-negative, asymptomatic obese subjects. Subjects were given omeprazole, rabeprazole or placebo in a randomized order and in a double-blind fashion. The main analysis criterion was 24-h percent of time post dose with intragastric pH above 3; secondary criteria were percentage of time above pH 4, median pH, [H+] concentrations and nocturnal acid breakthrough (NAB). Results were analyzed using linear mixed models and Wilks test comparing variances. 24-h median [IQ] percentages of time with gastric pH above 3 and 4 were higher with rabeprazole than omeprazole (46 [37-55] vs. 30 [15-55] %, 9 [5-11] % for placebo) but the differences did not reach statistical significance (p = 0.11 and 0.24, respectively). Median acid concentrations were significantly lower with rabeprazole than with omeprazole and placebo (22 [14-53] vs. 54 [19-130] and 95 [73-170] mmoles/l, p < 0.01) for all periods. The number of NAB was significantly lower with rabeprazole than with omeprazole (median 1 [1,2] vs. 2 [1-3], p = 0.04). Variances of 24-h data (pH above 3 and 4, median pH, [H+] concentrations) were significantly lower with rabeprazole than with omeprazole (p < 0.0001). In asymptomatic obese subjects the gastric antisecretory response to a single dose of rabeprazole and omeprazole was strong and not significantly different between drugs despite a significantly more homogeneous response with rabeprazole. ClinicalTrial.gov: NCT01136317.

A computational study of ultrafast acid dissociation and acid-base neutralization reactions. I. The model.

PubMed

Maurer, Patrick; Thomas, Vibin; Rivard, Ugo; Iftimie, Radu

2010-07-28

Ultrafast, time-resolved investigations of acid-base neutralization reactions have recently been performed using systems containing the photoacid 8-hydroxypyrene-1,3,6-trisulfonic acid trisodium salt (HPTS) and various Bronsted bases. Two conflicting neutralization mechanisms have been formulated by Mohammed et al. [Science 310, 83 (2005)] and Siwick et al. [J. Am. Chem. Soc. 129, 13412 (2007)] for the same acid-base system. Herein an ab initio molecular dynamics based computational model is formulated, which is able to investigate the validity of the proposed mechanisms in the general context of ground-state acid-base neutralization reactions. Our approach consists of using 2,4,6-tricyanophenol (exp. pKa congruent with 1) as a model for excited-state HPTS( *) (pKa congruent with 1.4) and carboxylate ions for the accepting base. We employ our recently proposed dipole-field/quantum mechanics (QM) treatment [P. Maurer and R. Iftimie, J. Chem. Phys. 132, 074112 (2010)] of the proton donor and acceptor molecules. This approach allows one to tune the free energy of neutralization to any desired value as well as model initial nonequilibrium hydration effects caused by a sudden increase in acidity, making it possible to achieve a more realistic comparison with experimental data than could be obtained via a full-QM treatment of the entire system. It is demonstrated that the dipole-field/QM model reproduces correctly key properties of the 2,4,6-tricyanophenol acid molecule including gas-phase proton dissociation energies and dipole moments, and condensed-phase hydration structure and pKa values.

Negligible effects of tryptophan on the aflatoxin adsorption of sodium bentonite.

PubMed

Magnoli, A P; Copia, P; Monge, M P; Magnoli, C E; Dalcero, A M; Chiacchiera, S M

2014-01-01

The main objective of this study was to determine if the competitive adsorption of tryptophan (Trp) and aflatoxin B₁ (AFB₁) could potentially affect the ability of a sodium bentonite (NaB) to prevent aflatoxicosis in monogastric animals. The adsorption of Trp and AFB₁ on this adsorbent is fast and could be operating on the same time-scale making competition feasible. In vitro competitive adsorption experiments under simulated gastrointestinal conditions were performed. A high affinity of the clay for Trp and NaB was observed. The effect of an excess of KCl to mimic the ionic strength of the physiological conditions were also investigated. A six-times decrease in the Trp surface excess at saturation was observed. A similar behaviour was previously found for AFB₁ adsorption. Taking into account the amount of Trp adsorbed by the clay and the usual adsorbent supplementation level in diets, a decrease in Trp bioavailability is not expected to occur. Tryptophan adsorption isotherms on NaB were 'S'-shaped and were adjusted by the Frumkin-Fowler-Guggenheim model. The reversibility of the adsorption processes was investigated in order to check a potential decrease in the ability of NaB to protect birds against chronic aflatoxicoses. Adsorption processes were completely reversible for Trp, while almost irreversible for AFB₁. In spite of the high affinity of the NaB for Trp, probably due to the reversible character of Trp adsorption, no changes in the AFB₁ adsorption isotherm were observed when an excess of the amino acid was added to the adsorption medium. As a consequence of the preferential and irreversible AFB₁ adsorption and the reversible weak binding of Trp to the NaB, no changes in the aflatoxin sorption ability of the clay are expected to occur in the gastrointestinal tract of birds.

What is the Ultimate Goal in Acid-Base Regulation?

ERIC Educational Resources Information Center

Balakrishnan, Selvakumar; Gopalakrishnan, Maya; Alagesan, Murali; Prakash, E. Sankaranarayanan

2007-01-01

It is common to see chapters on acid-base physiology state that the goal of acid-base regulatory mechanisms is to maintain the pH of arterial plasma and not arterial PCO [subscript 2] (Pa[subscript CO[subscript 2

Enhancing intracellular taxane delivery: current role and perspectives of nanoparticle albumin-bound paclitaxel in the treatment of advanced breast cancer.

PubMed

Guarneri, Valentina; Dieci, Maria Vittoria; Conte, Pierfranco

2012-02-01

Docetaxel and paclitaxel are among the most active agents for the treatment of breast cancer. These first-generation taxanes are extremely hydrophobic; therefore, solvents are needed for its parenteral administration. Albumin nanoparticle technology allows for the transportation of such hydrophobic drugs without the need of potentially toxic solvents. Nab-paclitaxel can be administered without premedication, in a shorter infusion time and without the need for a special infusion set. Moreover, this technology allows the selective delivery of larger amounts of anticancer drug to tumors, by exploiting endogenous albumin pathways. An overview of the albumin nanoparticle technology, from a clinical perspective, is reported in this paper. The preclinical and clinical development of nab-paclitaxel is reviewed, in the context of available therapies for advanced breast cancer, with a focus on safety data. Preclinical and clinical data on the prognostic and predictive role of SPARC (secreted protein, acidic and rich in cysteine) are also reported. Nab-paclitaxel is approved at present for the treatment of metastatic breast cancer, after the failure of first-line standard therapy, when anthracyclines are not indicated. Efficacy and safety data, along with a more convenient administration, confirm the potential for nab-paclitaxel to become a reference taxane in breast cancer treatment.

Cost-Benefit Analysis of Nanoparticle Albumin-Bound Paclitaxel versus Solvent-Based Paclitaxel for the Treatment of Metastatic Breast Cancer in the United States

NASA Astrophysics Data System (ADS)

Vichansavakul, Kittaya

Breast cancer is the second leading cause of death among women in the US. Although early detection and treatment help to increase survival rates, some unfortunate patients develop metastatic breast cancer that has no cure. Palliative treatment is the main objective in this group of patients in order to prolong life and reduce toxicities from interventions. In the advancement of treatment for metastatic breast cancer, solvent-based paclitaxel has been widely used. However, solvent-based paclitaxel often causes adverse reactions. Therefore, researchers have developed a new chemotherapy based on nanotechnology. One of these drugs is the Nanoparticle albumin-bound Paclitaxel. This nanodrug aims to increase therapeutic index by reducing adverse reactions from solvents and to improve efficacy of conventional cytotoxic chemotherapy. Breast cancer is a disease with high epidemiological and economic burden. The treatment of metastatic breast cancer has not only high direct costs but also high indirect costs. Breast cancer affects mass populations, especially women younger than 50 years of age. It relates to high indirect costs due to lost productivity and premature death because the majority of these patients are in the workforce. Because of the high cost of breast cancer therapies and short survival rates, the question is raised whether the costs and benefits are worth paying or not. Due to the rising costs in healthcare and new financing policies that have been developed to address this issue, economic evaluation is an important aspect of the development and use of any new interventions. To guide policy makers on how to allocate limited healthcare resources in the most efficient and effective manner, many economic evaluation methods can be used to measure the costs, benefits, and impacts of healthcare innovations. Currently, economic evaluation and health outcomes studies have focused greatly on cost-effectiveness and cost-utility analysis. However, the previous studies

Genomic Region Containing Toll-Like Receptor Genes Has a Major Impact on Total IgM Antibodies Including KLH-Binding IgM Natural Antibodies in Chickens

PubMed Central

Berghof, Tom V. L.; Visker, Marleen H. P. W.; Arts, Joop A. J.; Parmentier, Henk K.; van der Poel, Jan J.; Vereijken, Addie L. J.; Bovenhuis, Henk

2018-01-01

Natural antibodies (NAb) are antigen binding antibodies present in individuals without a previous exposure to this antigen. Keyhole limpet hemocyanin (KLH)-binding NAb levels were previously associated with survival in chickens. This suggests that selective breeding for KLH-binding NAb may increase survival by means of improved general disease resistance. Genome-wide association studies (GWAS) were performed to identify genes underlying genetic variation in NAb levels. The studied population consisted of 1,628 adolescent layer chickens with observations for titers of KLH-binding NAb of the isotypes IgM, IgA, IgG, the total KLH-binding (IgT) NAb titers, total antibody concentrations of the isotypes IgM, IgA, IgG, and the total antibodies concentration in plasma. GWAS were performed using 57,636 single-nucleotide polymorphisms (SNP). One chromosomal region on chromosome 4 was associated with KLH-binding IgT NAb, and total IgM concentration, and especially with KLH-binding IgM NAb. The region of interest was fine mapped by imputing the region of the study population to whole genome sequence, and subsequently performing an association study using the imputed sequence variants. 16 candidate genes were identified, of which FAM114A1, Toll-like receptor 1 family member B (TLR1B), TLR1A, Krüppel-like factor 3 (KLF3) showed the strongest associations. SNP located in coding regions of the candidate genes were checked for predicted changes in protein functioning. One SNP (at 69,965,939 base pairs) received the maximum impact score from two independent prediction tools, which makes this SNP the most likely causal variant. This SNP is located in TLR1A, which suggests a fundamental role of TLR1A on regulation of IgM levels (i.e., KLH-binding IgM NAb, and total IgM concentration), or B cells biology, or both. This study contributes to increased understanding of (genetic) regulation of KLH-binding NAb levels, and total antibody concentrations. PMID:29375555

Reactive Distillation for Esterification of Bio-based Organic Acids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fields, Nathan; Miller, Dennis J.; Asthana, Navinchandra S.

2008-09-23

The following is the final report of the three year research program to convert organic acids to their ethyl esters using reactive distillation. This report details the complete technical activities of research completed at Michigan State University for the period of October 1, 2003 to September 30, 2006, covering both reactive distillation research and development and the underlying thermodynamic and kinetic data required for successful and rigorous design of reactive distillation esterification processes. Specifically, this project has led to the development of economical, technically viable processes for ethyl lactate, triethyl citrate and diethyl succinate production, and on a larger scalemore » has added to the overall body of knowledge on applying fermentation based organic acids as platform chemicals in the emerging biorefinery. Organic acid esters constitute an attractive class of biorenewable chemicals that are made from corn or other renewable biomass carbohydrate feedstocks and replace analogous petroleum-based compounds, thus lessening U.S. dependence on foreign petroleum and enhancing overall biorefinery viability through production of value-added chemicals in parallel with biofuels production. Further, many of these ester products are candidates for fuel (particularly biodiesel) components, and thus will serve dual roles as both industrial chemicals and fuel enhancers in the emerging bioeconomy. The technical report from MSU is organized around the ethyl esters of four important biorenewables-based acids: lactic acid, citric acid, succinic acid, and propionic acid. Literature background on esterification and reactive distillation has been provided in Section One. Work on lactic acid is covered in Sections Two through Five, citric acid esterification in Sections Six and Seven, succinic acid in Section Eight, and propionic acid in Section Nine. Section Ten covers modeling of ester and organic acid vapor pressure properties using the SPEAD (Step

Thiol-Based Redox Switches and Gene Regulation

PubMed Central

2011-01-01

Abstract Cysteine is notable among the universal, proteinogenic amino acids for its facile redox chemistry. Cysteine thiolates are readily modified by reactive oxygen species (ROS), reactive electrophilic species (RES), and reactive nitrogen species (RNS). Although thiol switches are commonly triggered by disulfide bond formation, they can also be controlled by S-thiolation, S-alkylation, or modification by RNS. Thiol-based switches are common in both prokaryotic and eukaryotic organisms and activate functions that detoxify reactive species and restore thiol homeostasis while repressing functions that would be deleterious if expressed under oxidizing conditions. Here, we provide an overview of the best-understood examples of thiol-based redox switches that affect gene expression. Intra- or intermolecular disulfide bond formation serves as a direct regulatory switch for several bacterial transcription factors (OxyR, OhrR/2-Cys, Spx, YodB, CrtJ, and CprK) and indirectly regulates others (the RsrA anti-σ factor and RegB sensory histidine kinase). In eukaryotes, thiol-based switches control the yeast Yap1p transcription factor, the Nrf2/Keap1 electrophile and oxidative stress response, and the Chlamydomonas NAB1 translational repressor. Collectively, these regulators reveal a remarkable range of chemical modifications exploited by Cys residues to effect changes in gene expression. Antioxid. Redox Signal. 14, 1049—1063. PMID:20626317

Paediatric acid-base disorders: A case-based review of procedures and pitfalls

PubMed Central

Carmody, J Bryan; Norwood, Victoria F

2013-01-01

Acid-base disorders occur frequently in paediatric patients. Despite the perception that their analysis is complex and difficult, a straightforward set of rules is sufficient to interpret even the most complex disorders – provided certain pitfalls are avoided. Using a case-based approach, the present article reviews the fundamental concepts of acid-base analysis and highlights common mistakes and oversights. Specific topics include the proper identification of the primary disorder; distinguishing compensatory changes from additional primary disorders; use of the albumin-corrected anion gap to generate a differential diagnosis for patients with metabolic acidosis; screening for mixed disorders with the delta-delta formula; recognizing the limits of compensation; use of the anion gap to identify ‘hidden’ acidosis; and the importance of using information from the history and physical examination to identify the specific cause of a patient’s acid-base disturbance. PMID:24381489

Prebiotic synthesis of carboxylic acids, amino acids and nucleic acid bases from formamide under photochemical conditions⋆

NASA Astrophysics Data System (ADS)

Botta, Lorenzo; Mattia Bizzarri, Bruno; Piccinino, Davide; Fornaro, Teresa; Robert Brucato, John; Saladino, Raffaele

2017-07-01

The photochemical transformation of formamide in the presence of a mixture of TiO2 and ZnO metal oxides as catalysts afforded a large panel of molecules of biological relevance, including carboxylic acids, amino acids and nucleic acid bases. The reaction was less effective when performed in the presence of only one mineral, highlighting the role of synergic effects between the photoactive catalysts. Taken together, these results suggest that the synthesis of chemical precursors for both the genetic and the metabolic apparatuses might have occurred in a simple environment, consisting of formamide, photoactive metal oxides and UV-radiation.

The relationship between odd- and branched-chain fatty acids and microbial nucleic acid bases in rumen

PubMed Central

Liu, Keyuan; Hao, Xiaoyan; Li, Yang; Luo, Guobin; Zhang, Yonggen; Xin, Hangshu

2017-01-01

Objective This study aims to identify the relationship between odd- and branched-chain fatty acids (OBCFAs) and microbial nucleic acid bases in the rumen, and to establish a model to accurately predict microbial protein flow by using OBCFA. Methods To develop the regression equations, data on the rumen contents of individual cows were obtained from 2 feeding experiments. In the first experiment, 3 rumen-fistulated dry dairy cows arranged in a 3×3 Latin square were fed diets of differing forage to concentration ratios (F:C). The second experiment consisted of 9 lactating Holstein dairy cows of similar body weights at the same stage of pregnancy. For each lactation stage, 3 cows with similar milk production were selected. The rumen contents were sampled at 4 time points of every two hours after morning feeding 6 h, and then to analyse the concentrations of OBCFA and microbial nucleic acid bases in the rumen samples. Results The ruminal bacteria nucleic acid bases were significantly influenced by feeding diets of differing forge to concentration ratios and lactation stages of dairy cows (p<0.05). The concentrations of OBCFAs, especially odd-chain fatty acids and C15:0 isomers, strongly correlated with the microbial nucleic acid bases in the rumen (p<0.05). The equations of ruminal microbial nucleic acid bases established by ruminal OBCFAs contents showed a good predictive capacity, as indicated by reasonably low standard errors and high R-squared values. Conclusion This finding suggests that the rumen OBCFA composition could be used as an internal marker of rumen microbial matter. PMID:28728386

The relationship between odd- and branched-chain fatty acids and microbial nucleic acid bases in rumen.

PubMed

Liu, Keyuan; Hao, Xiaoyan; Li, Yang; Luo, Guobin; Zhang, Yonggen; Xin, Hangshu

2017-11-01

This study aims to identify the relationship between odd- and branched-chain fatty acids (OBCFAs) and microbial nucleic acid bases in the rumen, and to establish a model to accurately predict microbial protein flow by using OBCFA. To develop the regression equations, data on the rumen contents of individual cows were obtained from 2 feeding experiments. In the first experiment, 3 rumen-fistulated dry dairy cows arranged in a 3×3 Latin square were fed diets of differing forage to concentration ratios (F:C). The second experiment consisted of 9 lactating Holstein dairy cows of similar body weights at the same stage of pregnancy. For each lactation stage, 3 cows with similar milk production were selected. The rumen contents were sampled at 4 time points of every two hours after morning feeding 6 h, and then to analyse the concentrations of OBCFA and microbial nucleic acid bases in the rumen samples. The ruminal bacteria nucleic acid bases were significantly influenced by feeding diets of differing forge to concentration ratios and lactation stages of dairy cows (p<0.05). The concentrations of OBCFAs, especially odd-chain fatty acids and C15:0 isomers, strongly correlated with the microbial nucleic acid bases in the rumen (p<0.05). The equations of ruminal microbial nucleic acid bases established by ruminal OBCFAs contents showed a good predictive capacity, as indicated by reasonably low standard errors and high R-squared values. This finding suggests that the rumen OBCFA composition could be used as an internal marker of rumen microbial matter.

[Procedural analysis of acid-base balance disorder: case serials in 4 patents].

PubMed

Ma, Chunyuan; Wang, Guijie

2017-05-01

To establish the standardization process of acid-base balance analysis, analyze cases of acid-base balance disorder with the aid of acid-base balance coordinate graph. The acid-base balance theory were reviewed systematically on recent research progress, and the important concepts, definitions, formulas, parameters, regularity and inference in the analysis of acid-base balance were studied. The analysis of acid-base balance disordered processes and steps were figured. The application of acid-base balance coordinate graph in the cases was introduced. The method of "four parameters-four steps" analysis was put forward to analyze the acid-base balance disorders completely. "Four parameters" included pH, arterial partial pressure of carbon dioxide (PaCO 2 ), HCO 3 - and anion gap (AG). "Four steps" were outlined by following aspects: (1) according to the pH, PaCO 2 and HCO 3 - , the primary or main types of acid-base balance disorder was determined; (2) primary or main types of acid-base disorder were used to choose the appropriate compensation formula and to determine the presence of double mixed acid-base balance disorder; (3) the primary acid-base balance disorders were divided into two parts: respiratory acidosis or respiratory alkalosis, at the same time, the potential HCO 3 - should be calculated, the measured HCO 3 - should be replaced with potential HCO 3 - , to determine whether there were three mixed acid-base disorders; (4) based on the above analysis the data judged as the simple AG increased-metabolic acidosis was needed to be further analyzed. The ratio of ΔAG↑/ΔHCO 3 - ↓ was also needed to be calculated, to determine whether there was normal AG metabolic acidosis or metabolic alkalosis. In the clinical practice, PaCO 2 (as the abscissa) and HCO 3 - (as the ordinate) were used to establish a rectangular coordinate system, through origin (0, 0) and coordinate point (40, 24) could be a straight line, and all points on the straight line pH were equal

Human IgG lacking effector functions demonstrate lower FcRn-binding and reduced transplacental transport.

PubMed

Stapleton, Nigel M; Armstrong-Fisher, Sylvia S; Andersen, Jan Terje; van der Schoot, C Ellen; Porter, Charlene; Page, Kenneth R; Falconer, Donald; de Haas, Masja; Williamson, Lorna M; Clark, Michael R; Vidarsson, Gestur; Armour, Kathryn L

2018-03-01

We have previously generated human IgG1 antibodies that were engineered for reduced binding to the classical Fcγ receptors (FcγRI-III) and C1q, thereby eliminating their destructive effector functions (constant region G1Δnab). In their potential use as blocking agents, favorable binding to the neonatal Fc receptor (FcRn) is important to preserve the long half-life typical of IgG. An ability to cross the placenta, which is also mediated, at least in part, by FcRn is desirable in some indications, such as feto-maternal alloimmune disorders. Here, we show that G1Δnab mutants retain pH-dependent binding to human FcRn but that the amino acid alterations reduce the affinity of the IgG1:FcRn interaction by 2.0-fold and 1.6-fold for the two antibodies investigated. The transport of the modified G1Δnab mutants across monolayers of human cell lines expressing FcRn was approximately 75% of the wild-type, except that no difference was observed with human umbilical vein endothelial cells. G1Δnab mutation also reduced transport in an ex vivo placenta model. In conclusion, we demonstrate that, although the G1Δnab mutations are away from the FcRn-binding site, they have long-distance effects, modulating FcRn binding and transcellular transport. Our findings have implications for the design of therapeutic human IgG with tailored effector functions. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Prospects for nucleic acid-based therapeutics against hepatitis C virus.

PubMed

Lee, Chang Ho; Kim, Ji Hyun; Lee, Seong-Wook

2013-12-21

In this review, we discuss recent advances in nucleic acid-based therapeutic technologies that target hepatitis C virus (HCV) infection. Because the HCV genome is present exclusively in RNA form during replication, various nucleic acid-based therapeutic approaches targeting the HCV genome, such as ribozymes, aptamers, siRNAs, and antisense oligonucleotides, have been suggested as potential tools against HCV. Nucleic acids are potentially immunogenic and typically require a delivery tool to be utilized as therapeutics. These limitations have hampered the clinical development of nucleic acid-based therapeutics. However, despite these limitations, nucleic acid-based therapeutics has clinical value due to their great specificity, easy and large-scale synthesis with chemical methods, and pharmaceutical flexibility. Moreover, nucleic acid therapeutics are expected to broaden the range of targetable molecules essential for the HCV replication cycle, and therefore they may prove to be more effective than existing therapeutics, such as interferon-α and ribavirin combination therapy. This review focuses on the current status and future prospects of ribozymes, aptamers, siRNAs, and antisense oligonucleotides as therapeutic reagents against HCV.

Development of a tier 1 R5 clade C simian-human immunodeficiency virus as a tool to test neutralizing antibody-based immunoprophylaxis.

PubMed

Siddappa, Nagadenahalli B; Hemashettar, Girish; Wong, Yin Ling; Lakhashe, Samir; Rasmussen, Robert A; Watkins, Jennifer D; Novembre, Francis J; Villinger, François; Else, James G; Montefiori, David C; Ruprecht, Ruth M

2011-04-01

While some recently transmitted HIV clade C (HIV-C) strains exhibited tier 1 neutralization phenotypes, most were tier 2 strains (J Virol 2010; 84:1439). Because induction of neutralizing antibodies (nAbs) through vaccination against tier 2 viruses has proven difficult, we have generated a tier 1, clade C simian-human immunodeficiency virus (SHIV-C) to permit efficacy testing of candidate AIDS vaccines against tier 1 viruses. SHIV-1157ipEL was created by swapping env of a late-stage virus with that of a tier 1, early form. After adaptation to rhesus macaques (RM), passaged SHIV-1157ipEL-p replicated vigorously in vitro and in vivo while maintaining R5 tropism. The virus was reproducibly transmissible intrarectally. Phylogenetically, SHIV-1157ipEL-p Env clustered with HIV-C sequences. All RM chronically infected with SHIV-1157ipEL-p developed high nAb titers against autologous as well as heterologous tier 1 strains. SHIV-1157ipEL-p was reproducibly transmitted in RM, induced cross-clade nAbs, and represents a tool to evaluate anti-HIV-C nAb responses in primates. © 2010 John Wiley & Sons A/S.

Smoking and risk of treatment-induced neutralizing antibodies to interferon β-1a.

PubMed

Hedström, Anna Karin; Ryner, Malin; Fink, Katarina; Fogdell-Hahn, Anna; Alfredsson, Lars; Olsson, Tomas; Hillert, Jan

2014-04-01

Neutralizing antibodies (NAbs) to interferon β (IFNβ) products that develop during treatment are associated with a loss of clinical efficacy. The aim of this study was to investigate the influence of smoking habits on the risk of developing NAbs to IFNβ, in the treatment of multiple sclerosis (MS). This report is based on 695 MS patients treated with IFNβ-1a, included in two Swedish case-control studies that collected information on smoking habits. Using logistic regression, the development of NAbs to IFNβ-1a among current smokers was compared with that of non-smokers, by calculating the odds ratio (OR) with a 95% confidence interval (CI). Current smokers showed an increased risk of developing NAbs to IFNβ-1a, compared with non-smokers (OR 1.9; 95% CI 1.3-2.8; p = 0.002). There were no gender differences. We observed no association between past smoking and the risk of developing NAbs to IFNβ-1a. The finding that current smokers have an increased risk of developing NAbs to IFNβ-1a has implications, both for the practical care and the treatment of MS; it also provides an interesting perspective of the lungs as an immune-reactive organ, reacting upon irritation.

Lewis Acid-Base Chemistry of 7-Azaisoindigo-Based Organic Semiconductors.

PubMed

Randell, Nicholas M; Fransishyn, Kyle M; Kelly, Timothy L

2017-07-26

Low-band-gap organic semiconductors are important in a variety of organic electronics applications, such as organic photovoltaic devices, photodetectors, and field effect transistors. Building on our previous work, which introduced 7-azaisoindigo as an electron-deficient building block for the synthesis of donor-acceptor organic semiconductors, we demonstrate how Lewis acids can be used to further tune the energies of the frontier molecular orbitals. Coordination of a Lewis acid to the pyridinic nitrogen of 7-azaisoindigo greatly diminishes the electron density in the azaisoindigo π-system, resulting in a substantial reduction in the lowest unoccupied molecular orbital (LUMO) energy. This results in a smaller highest occupied molecular orbital-LUMO gap and shifts the lowest-energy electronic transition well into the near-infrared region. Both H + and BF 3 are shown to coordinate to azaisoindigo and affect the energy of the S 0 → S 1 transition. A combination of time-dependent density functional theory and UV/vis and 1 H NMR spectroscopic titrations reveal that when two azaisoindigo groups are present and high concentrations of acid are used, both pyridinic nitrogens bind Lewis acids. Importantly, we demonstrate that this acid-base chemistry can be carried out at the solid-vapor interface by exposing thin films of aza-substituted organic semiconductors to vapor-phase BF 3 ·Et 2 O. This suggests the possibility of using the BF 3 -bound 7-azaisoindigo-based semiconductors as n-type materials in various organic electronic applications.

Boronic acid-based chemical sensors for saccharides.

PubMed

Zhang, Xiao-Tai; Liu, Guang-Jian; Ning, Zhang-Wei; Xing, Guo-Wen

2017-11-27

During the past decades, the interaction between boronic acids-functionalized sensors and saccharides is of great interest in the frontier domain of the interdiscipline concerning both biology and chemistry. Various boronic acid-based sensing systems have been developed to detect saccharides and corresponding derivatives in vitro as well as in vivo, which embrace unimolecular sensors, two-component sensing ensembles, functional assemblies, and boronic acid-loaded nanomaterials or surfaces. New sensing strategies emerge in endlessly with excellent selectivity and sensitivity. In this review, several typical sensing systems were introduced and some promising examples were highlighted to enable the deep insight of saccharides sensing on the basis of boronic acids. Copyright © 2017 Elsevier Ltd. All rights reserved.

Elicitation of Robust Tier 2 Neutralizing Antibody Responses in Nonhuman Primates by HIV Envelope Trimer Immunization Using Optimized Approaches.

PubMed

Pauthner, Matthias; Havenar-Daughton, Colin; Sok, Devin; Nkolola, Joseph P; Bastidas, Raiza; Boopathy, Archana V; Carnathan, Diane G; Chandrashekar, Abishek; Cirelli, Kimberly M; Cottrell, Christopher A; Eroshkin, Alexey M; Guenaga, Javier; Kaushik, Kirti; Kulp, Daniel W; Liu, Jinyan; McCoy, Laura E; Oom, Aaron L; Ozorowski, Gabriel; Post, Kai W; Sharma, Shailendra K; Steichen, Jon M; de Taeye, Steven W; Tokatlian, Talar; Torrents de la Peña, Alba; Butera, Salvatore T; LaBranche, Celia C; Montefiori, David C; Silvestri, Guido; Wilson, Ian A; Irvine, Darrell J; Sanders, Rogier W; Schief, William R; Ward, Andrew B; Wyatt, Richard T; Barouch, Dan H; Crotty, Shane; Burton, Dennis R

2017-06-20

The development of stabilized recombinant HIV envelope trimers that mimic the virion surface molecule has increased enthusiasm for a neutralizing antibody (nAb)-based HIV vaccine. However, there is limited experience with recombinant trimers as immunogens in nonhuman primates, which are typically used as a model for humans. Here, we tested multiple immunogens and immunization strategies head-to-head to determine their impact on the quantity, quality, and kinetics of autologous tier 2 nAb development. A bilateral, adjuvanted, subcutaneous immunization protocol induced reproducible tier 2 nAb responses after only two immunizations 8 weeks apart, and these were further enhanced by a third immunization with BG505 SOSIP trimer. We identified immunogens that minimized non-neutralizing V3 responses and demonstrated that continuous immunogen delivery could enhance nAb responses. nAb responses were strongly associated with germinal center reactions, as assessed by lymph node fine needle aspiration. This study provides a framework for preclinical and clinical vaccine studies targeting nAb elicitation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Budding yeast telomerase RNA transcription termination is dictated by the Nrd1/Nab3 non-coding RNA termination pathway

PubMed Central

Noël, Jean-François; Larose, Stéphanie; Abou Elela, Sherif; Wellinger, Raymund J.

2012-01-01

The RNA component of budding yeast telomerase (Tlc1) occurs in two forms, a non-polyadenylated form found in functional telomerase and a rare polyadenylated version with unknown function. Previous work suggested that the functional Tlc1 polyA− RNA is processed from the polyA+ form, but the mechanisms regulating its transcription termination and 3′-end formation remained unclear. Here we examined transcription termination of Tlc1 RNA in the sequences 3′ of the TLC1 gene and relate it to telomere maintenance. Strikingly, disruption of all probable or cryptic polyadenylation signals near the 3′-end blocked the accumulation of the previously reported polyA+ RNA without affecting the level, function or specific 3′ nucleotide of the mature polyA− form. A genetic approach analysing TLC1 3′-end sequences revealed that transcription terminates upstream of the polyadenylation sites. Furthermore, the results also demonstrate that the function of this Tlc1 terminator depends on the Nrd1/Nab3 transcription termination pathway. The data thus show that transcription termination of the budding yeast telomerase RNA occurs as that of snRNAs and Tlc1 functions in telomere maintenance are not strictly dependent on a polyadenylated precursor, even if the polyA+ form can serve as intermediate in a redundant termination/maturation pathway. PMID:22379137

Evaluating Interest in Acids-Bases: Development of an Acid-Base Interest Scale (ABIS) and Assessment of Pre-Service Science Teachers' Interest

ERIC Educational Resources Information Center

Çiçek, Ö.; Ilhan, N.

2017-01-01

Students are more likely to be successful in topics they are interested in than others. This study aims to develop an Acid-Base Interest Scale (ABIS) and subsequently evaluate the interest of pre-service science teachers in acids-bases according to gender, years at the university, type of high school the pre-service science teachers attended, and…

Soluble adenylyl cyclase is an acid-base sensor in epithelial base-secreting cells.

PubMed

Roa, Jinae N; Tresguerres, Martin

2016-08-01

Blood acid-base regulation by specialized epithelia, such as gills and kidney, requires the ability to sense blood acid-base status. Here, we developed primary cultures of ray (Urolophus halleri) gill cells to study mechanisms for acid-base sensing without the interference of whole animal hormonal regulation. Ray gills have abundant base-secreting cells, identified by their noticeable expression of vacuolar-type H(+)-ATPase (VHA), and also express the evolutionarily conserved acid-base sensor soluble adenylyl cyclase (sAC). Exposure of cultured cells to extracellular alkalosis (pH 8.0, 40 mM HCO3 (-)) triggered VHA translocation to the cell membrane, similar to previous reports in live animals experiencing blood alkalosis. VHA translocation was dependent on sAC, as it was blocked by the sAC-specific inhibitor KH7. Ray gill base-secreting cells also express transmembrane adenylyl cyclases (tmACs); however, tmAC inhibition by 2',5'-dideoxyadenosine did not prevent alkalosis-dependent VHA translocation, and tmAC activation by forskolin reduced the abundance of VHA at the cell membrane. This study demonstrates that sAC is a necessary and sufficient sensor of extracellular alkalosis in ray gill base-secreting cells. In addition, this study indicates that different sources of cAMP differentially modulate cell biology. Copyright © 2016 the American Physiological Society.

Respiratory Acid-Base Disorders in the Critical Care Unit.

PubMed

Hopper, Kate

2017-03-01

The incidence of respiratory acid-base abnormalities in the critical care unit (CCU) is unknown, although respiratory alkalosis is suspected to be common in this population. Abnormal carbon dioxide tension can have many physiologic effects, and changes in Pco 2 may have a significant impact on outcome. Monitoring Pco 2 in CCU patients is an important aspect of critical patient assessment, and identification of respiratory acid-base abnormalities can be valuable as a diagnostic tool. Treatment of respiratory acid-base disorders is largely focused on resolution of the primary disease, although mechanical ventilation may be indicated in cases with severe respiratory acidosis. Published by Elsevier Inc.

Respiratory Adaptations in Acid-base Disturbances: Role of Cerebral Fluids,

DTIC Science & Technology

1979-06-19

The respiratory and metabolic components of acid-base homeostasis are defined. A quantitative empirical description of the (incomplete) mutual...literature. Respiratory adaptations in steady acid-base disturbances of metabolic origin (hyperventilation with hypocapnia in primary metabolic acidosis, and...hypoventilation with hypercapnia in metabolic alkalosis ) are analyzed as a function of the acidity of the cerebral fluids (cerebrospinal and cerebral interstitial fluid). (Author)

Acid-base equilibria inside amine-functionalized mesoporous silica.

PubMed

Yamaguchi, Akira; Namekawa, Manato; Kamijo, Toshio; Itoh, Tetsuji; Teramae, Norio

2011-04-15

Acid-base equilibria and effective proton concentration inside a silica mesopore modified with a trimethyl ammonium (TMAP) layer were studied by steady-state fluorescence experiments. The mesoporous silica with a dense TMAP layer (1.4 molecules/nm(2)) was prepared by a post grafting of N-trimethoxysilylpropyl-N,N,N-trimethylammonium at surfactant-templated mesoporous silica (diameter of silica framework =3.1 nm). The resulting TMAP-modified mesoporous silica strongly adsorbed of anionic fluorescence indicator dyes (8-hydroxypyrene-1,3,6-trisulfonate (pyranine), 8-aminopyrene-1,3,6-trisulfonate (APTS), 5,10,15,20-tetraphenyl-21H,23H-porphinetetrasulfonic acid disulfuric acid (TPPS), 2-naphthol-3,6-disulfonate (2NT)) and fluorescence excitation spectra of these dyes within TMAP-modified mesoporous silica were measured by varying the solution pH. The fluorescence experiments revealed that the acid-base equilibrium reactions of all pH indicator dyes within the TMAP-modified silica mesopore were quite different from those in bulk water. From the analysis of the acid-base equilibrium of pyranine, the following relationships between solution pH (pH(bulk)) and the effective proton concentration inside the pore (pH(pore)) were obtained: (1) shift of pH(pore) was 1.8 (ΔpH(pore)=1.8) for the pH(bulk) change from 2.1 to 9.1 (ΔpH(bulk)=7.0); (2) pH(pore) was not simply proportional to pH(bulk); (3) the inside of the TMAP-modified silica mesopore was suggested to be in a weak acidic or neutral condition when pH(bulk) was changed from 2.0 to 9.1. Since these relationships between pH(bulk) and pH(pore) could explain the acid-base equilibria of other pH indicator dyes (APTS, TPPS, 2NT), these relationships were inferred to describe the effective proton concentration inside the TMAP-modified silica mesopore. © 2011 American Chemical Society

Synthesis and antimicrobial activities of new higher amino acid Schiff base derivatives of 6-aminopenicillanic acid and 7-aminocephalosporanic acid

NASA Astrophysics Data System (ADS)

Özdemir (nee Güngör), Özlem; Gürkan, Perihan; Özçelik, Berrin; Oyardı, Özlem

2016-02-01

Novel β-lactam derivatives (1c-3c) (1d-3d) were produced by using 6-aminopenicillanic acid (6-APA), 7-aminocephalosporanic acid (7-ACA) and the higher amino acid Schiff bases. The synthesized compounds were characterized by elemental analysis, IR, 1H/13C NMR and UV-vis spectra. Antibacterial activities of all the higher amino acid Schiff bases (1a-3a) (1b-3b) and β-lactam derivatives were screened against three gram negative bacteria (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Acinetobacter baumannii RSKK 02026), three gram positive bacteria (Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 07005, Bacillus subtilis ATCC 6633) and their drug-resistant isolates by using broth microdilution method. Two fungi (Candida albicans and Candida krusei) were used for antifungal activity.

Syntheses, structural, computational, and thermal analysis of acid-base complexes of picric acid with N-heterocyclic bases.

PubMed

Goel, Nidhi; Singh, Udai P

2013-10-10

Four new acid-base complexes using picric acid [(OH)(NO2)3C6H2] (PA) and N-heterocyclic bases (1,10-phenanthroline (phen)/2,2';6',2"-terpyridine (terpy)/hexamethylenetetramine (hmta)/2,4,6-tri(2-pyridyl)-1,3,5-triazine (tptz)) were prepared and characterized by elemental analysis, IR, NMR and X-ray crystallography. Crystal structures provide detailed information of the noncovalent interactions present in different complexes. The optimized structures of the complexes were calculated in terms of the density functional theory. The thermolysis of these complexes was investigated by TG-DSC and ignition delay measurements. The model-free isoconversional and model-fitting kinetic approaches have been applied to isothermal TG data for kinetics investigation of thermal decomposition of these complexes.

TRANSFUSIONS—Hazardous Acid-Base Changes with Citrated Blood

PubMed Central

Pedro, Jovita M. San; Iwai, Seizo; Hattori, Mitsuo; Leigh, M. Digby

1962-01-01

In a study of the acid-base changes in the blood of rabbits during and following transfusions of citrated blood and of heparinized blood, it was observed that, with citrated blood, pH decreased and carbon dioxide tensions rose. With heparinized blood, the acid-base balance was maintained within normal limits following transfusions. The potential hazards of rapid massive citrated blood transfusions in the anesthetized patient during operation must be kept in mind. PMID:14496706

Selected HIV-1 Env Trimeric Formulations Act as Potent Immunogens in a Rabbit Vaccination Model

PubMed Central

Heyndrickx, Leo; Stewart-Jones, Guillaume; Jansson, Marianne; Schuitemaker, Hanneke; Bowles, Emma; Buonaguro, Luigi; Grevstad, Berit; Vinner, Lasse; Vereecken, Katleen; Parker, Joe; Ramaswamy, Meghna; Biswas, Priscilla; Vanham, Guido; Scarlatti, Gabriella; Fomsgaard, Anders

2013-01-01

Background Ten to 30% of HIV-1 infected subjects develop broadly neutralizing antibodies (bNAbs) during chronic infection. We hypothesized that immunizing rabbits with viral envelope glycoproteins (Envs) from these patients may induce bNAbs, when formulated as a trimeric protein and in the presence of an adjuvant. Methods Based on in vitro neutralizing activity in serum, patients with bNAbs were selected for cloning of their HIV-1 Env. Seven stable soluble trimeric gp140 proteins were generated from sequences derived from four adults and two children infected with either clade A or B HIV-1. From one of the clade A Envs both the monomeric and trimeric Env were produced for comparison. Rabbits were immunized with soluble gp120 or trimeric gp140 proteins in combination with the adjuvant dimethyl dioctadecyl ammonium/trehalose dibehenate (CAF01). Env binding in rabbit immune serum was determined using ELISAs based on gp120-IIIB protein. Neutralizing activity of IgG purified from rabbit immune sera was measured with the pseudovirus-TZMbl assay and a PBMC-based neutralization assay for selected experiments. Results It was initially established that gp140 trimers induce better antibody responses over gp120 monomers and that the adjuvant CAF01 was necessary for such strong responses. Gp140 trimers, based on HIV-1 variants from patients with bNAbs, were able to elicit both gp120IIIB specific IgG and NAbs to Tier 1 viruses of different subtypes. Potency of NAbs closely correlated with titers, and an gp120-binding IgG titer above a threshold of 100,000 was predictive of neutralization capability. Finally, peptide inhibition experiments showed that a large fraction of the neutralizing IgG was directed against the gp120 V3 region. Conclusions Our results indicate that the strategy of reverse immunology based on selected Env sequences is promising when immunogens are delivered as stabilized trimers in CAF01 adjuvant and that the rabbit is a valuable model for HIV vaccine studies

Selected HIV-1 Env trimeric formulations act as potent immunogens in a rabbit vaccination model.

PubMed

Heyndrickx, Leo; Stewart-Jones, Guillaume; Jansson, Marianne; Schuitemaker, Hanneke; Bowles, Emma; Buonaguro, Luigi; Grevstad, Berit; Vinner, Lasse; Vereecken, Katleen; Parker, Joe; Ramaswamy, Meghna; Biswas, Priscilla; Vanham, Guido; Scarlatti, Gabriella; Fomsgaard, Anders

2013-01-01

Ten to 30% of HIV-1 infected subjects develop broadly neutralizing antibodies (bNAbs) during chronic infection. We hypothesized that immunizing rabbits with viral envelope glycoproteins (Envs) from these patients may induce bNAbs, when formulated as a trimeric protein and in the presence of an adjuvant. Based on in vitro neutralizing activity in serum, patients with bNAbs were selected for cloning of their HIV-1 Env. Seven stable soluble trimeric gp140 proteins were generated from sequences derived from four adults and two children infected with either clade A or B HIV-1. From one of the clade A Envs both the monomeric and trimeric Env were produced for comparison. Rabbits were immunized with soluble gp120 or trimeric gp140 proteins in combination with the adjuvant dimethyl dioctadecyl ammonium/trehalose dibehenate (CAF01). Env binding in rabbit immune serum was determined using ELISAs based on gp120-IIIB protein. Neutralizing activity of IgG purified from rabbit immune sera was measured with the pseudovirus-TZMbl assay and a PBMC-based neutralization assay for selected experiments. It was initially established that gp140 trimers induce better antibody responses over gp120 monomers and that the adjuvant CAF01 was necessary for such strong responses. Gp140 trimers, based on HIV-1 variants from patients with bNAbs, were able to elicit both gp120IIIB specific IgG and NAbs to Tier 1 viruses of different subtypes. Potency of NAbs closely correlated with titers, and an gp120-binding IgG titer above a threshold of 100,000 was predictive of neutralization capability. Finally, peptide inhibition experiments showed that a large fraction of the neutralizing IgG was directed against the gp120 V3 region. Our results indicate that the strategy of reverse immunology based on selected Env sequences is promising when immunogens are delivered as stabilized trimers in CAF01 adjuvant and that the rabbit is a valuable model for HIV vaccine studies.

Hard and soft acids and bases: atoms and atomic ions.

PubMed

Reed, James L

2008-07-07

The structural origin of hard-soft behavior in atomic acids and bases has been explored using a simple orbital model. The Pearson principle of hard and soft acids and bases has been taken to be the defining statement about hard-soft behavior and as a definition of chemical hardness. There are a number of conditions that are imposed on any candidate structure and associated property by the Pearson principle, which have been exploited. The Pearson principle itself has been used to generate a thermodynamically based scale of relative hardness and softness for acids and bases (operational chemical hardness), and a modified Slater model has been used to discern the electronic origin of hard-soft behavior. Whereas chemical hardness is a chemical property of an acid or base and the operational chemical hardness is an experimental measure of it, the absolute hardness is a physical property of an atom or molecule. A critical examination of chemical hardness, which has been based on a more rigorous application of the Pearson principle and the availability of quantitative measures of chemical hardness, suggests that the origin of hard-soft behavior for both acids and bases resides in the relaxation of the electrons not undergoing transfer during the acid-base interaction. Furthermore, the results suggest that the absolute hardness should not be taken as synonymous with chemical hardness but that the relationship is somewhat more complex. Finally, this work provides additional groundwork for a better understanding of chemical hardness that will inform the understanding of hardness in molecules.

The Roles of Acids and Bases in Enzyme Catalysis

ERIC Educational Resources Information Center

Weiss, Hilton M.

2007-01-01

Many organic reactions are catalyzed by strong acids or bases that protonate or deprotonate neutral reactants leading to reactive cations or anions that proceed to products. In enzyme reactions, only weak acids and bases are available to hydrogen bond to reactants and to transfer protons in response to developing charges. Understanding this…

Nucleic acid based fluorescent sensor for mercury detection

DOEpatents

Lu, Yi; Liu, Juewen

2013-02-05

A nucleic acid enzyme comprises an oligonucleotide containing thymine bases. The nucleic acid enzyme is dependent on both Hg.sup.2+and a second ion as cofactors, to produce a product from a substrate. The substrate comprises a ribonucleotide, a deoxyribonucleotide, or both.

Complexity in Acid–Base Titrations: Multimer Formation Between Phosphoric Acids and Imines

PubMed Central

Malm, Christian; Kim, Heejae; Wagner, Manfred

2017-01-01

Abstract Solutions of Brønsted acids with bases in aprotic solvents are not only common model systems to study the fundamentals of proton transfer pathways but are also highly relevant to Brønsted acid catalysis. Despite their importance the light nature of the proton makes characterization of acid–base aggregates challenging. Here, we track such acid–base interactions over a broad range of relative compositions between diphenyl phosphoric acid and the base quinaldine in dichloromethane, by using a combination of dielectric relaxation and NMR spectroscopy. In contrast to what one would expect for an acid–base titration, we find strong deviations from quantitative proton transfer from the acid to the base. Even for an excess of the base, multimers consisting of one base and at least two acid molecules are formed, in addition to the occurrence of proton transfer from the acid to the base and simultaneous formation of ion pairs. For equimolar mixtures such multimers constitute about one third of all intermolecular aggregates. Quantitative analysis of our results shows that the acid‐base association constant is only around six times larger than that for the acid binding to an acid‐base dimer, that is, to an already protonated base. Our findings have implications for the interpretation of previous studies of reactive intermediates in organocatalysis and provide a rationale for previously observed nonlinear effects in phosphoric acid catalysis. PMID:28597513

Structure and functioning of the acid-base system in the Baltic Sea

NASA Astrophysics Data System (ADS)

Kuliński, Karol; Schneider, Bernd; Szymczycha, Beata; Stokowski, Marcin

2017-12-01

The marine acid-base system is relatively well understood for oceanic waters. Its structure and functioning is less obvious for the coastal and shelf seas due to a number of regionally specific anomalies. In this review article we collect and integrate existing knowledge of the acid-base system in the Baltic Sea. Hydrographical and biogeochemical characteristics of the Baltic Sea, as manifested in horizontal and vertical salinity gradients, permanent stratification of the water column, eutrophication, high organic-matter concentrations and high anthropogenic pressure, make the acid-base system complex. In this study, we summarize the general knowledge of the marine acid-base system as well as describe the peculiarities identified and reported for the Baltic Sea specifically. In this context we discuss issues such as dissociation constants in brackish water, different chemical alkalinity models including contributions by organic acid-base systems, long-term changes in total alkalinity, anomalies of borate alkalinity, and the acid-base effects of biomass production and mineralization. Finally, we identify research gaps and specify limitations concerning the Baltic Sea acid-base system.

Acid-Base Chemistry of White Wine: Analytical Characterisation and Chemical Modelling

PubMed Central

Prenesti, Enrico; Berto, Silvia; Toso, Simona; Daniele, Pier Giuseppe

2012-01-01

A chemical model of the acid-base properties is optimized for each white wine under study, together with the calculation of their ionic strength, taking into account the contributions of all significant ionic species (strong electrolytes and weak one sensitive to the chemical equilibria). Coupling the HPLC-IEC and HPLC-RP methods, we are able to quantify up to 12 carboxylic acids, the most relevant substances responsible of the acid-base equilibria of wine. The analytical concentration of carboxylic acids and of other acid-base active substances was used as input, with the total acidity, for the chemical modelling step of the study based on the contemporary treatment of overlapped protonation equilibria. New protonation constants were refined (L-lactic and succinic acids) with respect to our previous investigation on red wines. Attention was paid for mixed solvent (ethanol-water mixture), ionic strength, and temperature to ensure a thermodynamic level to the study. Validation of the chemical model optimized is achieved by way of conductometric measurements and using a synthetic “wine” especially adapted for testing. PMID:22566762

Acid-base chemistry of white wine: analytical characterisation and chemical modelling.

PubMed

Prenesti, Enrico; Berto, Silvia; Toso, Simona; Daniele, Pier Giuseppe

2012-01-01

A chemical model of the acid-base properties is optimized for each white wine under study, together with the calculation of their ionic strength, taking into account the contributions of all significant ionic species (strong electrolytes and weak one sensitive to the chemical equilibria). Coupling the HPLC-IEC and HPLC-RP methods, we are able to quantify up to 12 carboxylic acids, the most relevant substances responsible of the acid-base equilibria of wine. The analytical concentration of carboxylic acids and of other acid-base active substances was used as input, with the total acidity, for the chemical modelling step of the study based on the contemporary treatment of overlapped protonation equilibria. New protonation constants were refined (L-lactic and succinic acids) with respect to our previous investigation on red wines. Attention was paid for mixed solvent (ethanol-water mixture), ionic strength, and temperature to ensure a thermodynamic level to the study. Validation of the chemical model optimized is achieved by way of conductometric measurements and using a synthetic "wine" especially adapted for testing.

Lewis base activation of Lewis acids: development of a Lewis base catalyzed selenolactonization.

PubMed

Denmark, Scott E; Collins, William R

2007-09-13

The concept of Lewis base activation of Lewis acids has been applied to the selenolactonization reaction. Through the use of substoichiometric amounts of Lewis bases with "soft" donor atoms (S, Se, P) significant rate enhancements over the background reaction are seen. Preliminary mechanistic investigations have revealed the resting state of the catalyst as well as the significance of a weak Brønsted acid promoter.

Crystal and molecular structure of eight organic acid-base adducts from 2-methylquinoline and different acids

NASA Astrophysics Data System (ADS)

Zhang, Jing; Jin, Shouwen; Tao, Lin; Liu, Bin; Wang, Daqi

2014-08-01

Eight supramolecular complexes with 2-methylquinoline and acidic components as 4-aminobenzoic acid, 2-aminobenzoic acid, salicylic acid, 5-chlorosalicylic acid, 3,5-dinitrosalicylic acid, malic acid, sebacic acid, and 1,5-naphthalenedisulfonic acid were synthesized and characterized by X-ray crystallography, IR, mp, and elemental analysis. All of the complexes are organic salts except compound 2. All supramolecular architectures of 1-8 involve extensive classical hydrogen bonds as well as other noncovalent interactions. The results presented herein indicate that the strength and directionality of the classical hydrogen bonds (ionic or neutral) between acidic components and 2-methylquinoline are sufficient to bring about the formation of binary organic acid-base adducts. The role of weak and strong noncovalent interactions in the crystal packing is ascertained. These weak interactions combined, the complexes 1-8 displayed 2D-3D framework structure.

A Clinical Approach to the Diagnosis of Acid-Base Disorders

PubMed Central

Bear, Robert A.

1986-01-01

The ability to diagnose and manage acid-base disorders rapidly and effectively is essential to the care of critically ill patients. This article presents an approach to the diagnosis of pure and mixed acid-base disorders, metabolic or respiratory. The approach taken is based on using the law of mass-action equation as it applies to the bicarbonate buffer system (Henderson equation), using sub-classifications for diagnostic purposes of causes of metabolic acidosis and metabolic alkalosis, and using a knowledge of the well-defined and predictable compensatory responses that attempt to limit the change in pH in each of the primary acid-base disorders. PMID:21267134

Nucleic acid-based nanoengineering: novel structures for biomedical applications

PubMed Central

Li, Hanying; LaBean, Thomas H.; Leong, Kam W.

2011-01-01

Nanoengineering exploits the interactions of materials at the nanometre scale to create functional nanostructures. It relies on the precise organization of nanomaterials to achieve unique functionality. There are no interactions more elegant than those governing nucleic acids via Watson–Crick base-pairing rules. The infinite combinations of DNA/RNA base pairs and their remarkable molecular recognition capability can give rise to interesting nanostructures that are only limited by our imagination. Over the past years, creative assembly of nucleic acids has fashioned a plethora of two-dimensional and three-dimensional nanostructures with precisely controlled size, shape and spatial functionalization. These nanostructures have been precisely patterned with molecules, proteins and gold nanoparticles for the observation of chemical reactions at the single molecule level, activation of enzymatic cascade and novel modality of photonic detection, respectively. Recently, they have also been engineered to encapsulate and release bioactive agents in a stimulus-responsive manner for therapeutic applications. The future of nucleic acid-based nanoengineering is bright and exciting. In this review, we will discuss the strategies to control the assembly of nucleic acids and highlight the recent efforts to build functional nucleic acid nanodevices for nanomedicine. PMID:23050076

Characterization of broadly neutralizing antibody responses to HIV-1 in a cohort of long term non-progressors.

PubMed

González, Nuria; McKee, Krisha; Lynch, Rebecca M; Georgiev, Ivelin S; Jimenez, Laura; Grau, Eulalia; Yuste, Eloísa; Kwong, Peter D; Mascola, John R; Alcamí, José

2018-01-01

Only a small fraction of HIV-1-infected patients develop broadly neutralizing antibodies (bNAbs), a process generally associated to chronic antigen stimulation. It has been described that rare aviremic HIV-1-infected patients can generate bNAbs but this issue remains controversial. To address this matter we have assessed bNAb responses in a large cohort of long-term non-progressors (LTNPs) with low or undetectable viremia. Samples from the LTNP cohort of the Spanish AIDS Research Network (87 elite and 42 viremic controllers) and a control population of 176 viremic typical-progressors (TPs) were screened for bNAbs using Env-recombinant viruses. bNAb specificities were studied by ELISA using mutated gp120, neutralization assays with mutated viruses, and peptide competition. Epitope specificities were also elucidated from the serum pattern of neutralization against a panel of diverse HIV-1 isolates. Broadly neutralizing sera were found among 9.3% LTNPs, both elite (7%) and viremic controllers (14%). Within the broadly neutralizing sera, CD4 binding site antibodies were detected by ELISA in 4/12 LTNPs (33%), and 16/33 of TPs (48%). Anti-MPER antibodies were detected in 6/12 LTNPs (50%) and 14/33 TPs (42%) whereas glycan-dependent HIV-1 bNAbs were more frequent in LTNPs (11/12, 92%) as compared to TPs (12/33, 36%). A good concordance between standard serum mapping and neutralization-based mapping was observed. LTNPs, both viremic and elite controllers, showed broad humoral immune responses against HIV-1, including activity against many major epitopes involved in bNAbs-mediated protection.

Environmental and Chemical Aging of Fatty-Acid-Based Vinyl Ester Composites

DTIC Science & Technology

2011-04-01

Environmental and Chemical Aging of Fatty- Acid -Based Vinyl Ester Composites by Steven E. Boyd and John J. La Scala ARL-TR-5523 April...2011 Environmental and Chemical Aging of Fatty- Acid -Based Vinyl Ester Composites Steven E. Boyd and John J. La Scala Weapons and Materials...COVERED (From - To) October 2009–September 2010 4. TITLE AND SUBTITLE Environmental and Chemical Aging of Fatty- Acid -Based Vinyl Ester Composites

Natural Humic-Acid-Based Phototheranostic Agent.

PubMed

Miao, Zhao-Hua; Li, Kai; Liu, Pei-Ying; Li, Zhenglin; Yang, Huanjie; Zhao, Qingliang; Chang, Manli; Yang, Qingzhu; Zhen, Liang; Xu, Cheng-Yan

2018-04-01

Humic acids, a major constituent of natural organic carbon resources, are naturally formed through the microbial biodegradation of animal and plant residues. Due to numerous physiologically active groups (phenol, carboxyl, and quinone), the biomedical applications of humic acid have been already investigated across different cultures for several centuries or even longer. In this work, sodium humate, the sodium salt of humic acid, is explored as phototheranostic agent for light-induced photoacoustic imaging and photothermal therapy based on intrinsic absorption in the near-infrared region. The purified colloidal sodium humate exhibits a high photothermal conversion efficiency up to 76.3%, much higher than that of the majority of state-of-the-art photothermal agents including gold nanorods, Cu 9 S 5 nanoparticles, antimonene quantum dots, and black phosphorus quantum dots, leading to obvious photoacoustic enhancement in vitro and in vivo. Besides, highly effective photothermal ablation of HeLa tumor is achieved through intratumoral injection. Impressively, sodium humate reveals ultralow toxicity at the cellular and animal levels. This work promises the great potential of humic acids as light-mediated theranostic agents, thus expanding the application scope of traditional humic acids in biomedical field. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A comparative genomics perspective on the genetic content of the alkaliphilic haloarchaeon Natrialba magadii ATCC 43099T

PubMed Central

2012-01-01

Background Natrialba magadii is an aerobic chemoorganotrophic member of the Euryarchaeota and is a dual extremophile requiring alkaline conditions and hypersalinity for optimal growth. The genome sequence of Nab. magadii type strain ATCC 43099 was deciphered to obtain a comprehensive insight into the genetic content of this haloarchaeon and to understand the basis of some of the cellular functions necessary for its survival. Results The genome of Nab. magadii consists of four replicons with a total sequence of 4,443,643 bp and encodes 4,212 putative proteins, some of which contain peptide repeats of various lengths. Comparative genome analyses facilitated the identification of genes encoding putative proteins involved in adaptation to hypersalinity, stress response, glycosylation, and polysaccharide biosynthesis. A proton-driven ATP synthase and a variety of putative cytochromes and other proteins supporting aerobic respiration and electron transfer were encoded by one or more of Nab. magadii replicons. The genome encodes a number of putative proteases/peptidases as well as protein secretion functions. Genes encoding putative transcriptional regulators, basal transcription factors, signal perception/transduction proteins, and chemotaxis/phototaxis proteins were abundant in the genome. Pathways for the biosynthesis of thiamine, riboflavin, heme, cobalamin, coenzyme F420 and other essential co-factors were deduced by in depth sequence analyses. However, approximately 36% of Nab. magadii protein coding genes could not be assigned a function based on Blast analysis and have been annotated as encoding hypothetical or conserved hypothetical proteins. Furthermore, despite extensive comparative genomic analyses, genes necessary for survival in alkaline conditions could not be identified in Nab. magadii. Conclusions Based on genomic analyses, Nab. magadii is predicted to be metabolically versatile and it could use different carbon and energy sources to sustain growth. Nab

Amino acid-based zwitterionic polymers: antifouling properties and low cytotoxicity.

PubMed

Li, Wenchen; Liu, Qingsheng; Liu, Lingyun

2014-01-01

A group of five amino acid containing zwitterionic vinyl monomers, based on serine, lysine, ornithine, glutamic acid, and aspartic acid, respectively, were proposed and developed for potential antifouling applications. Their polymer brushes were grafted on gold chips by surface-initiated photoiniferter-mediated polymerization. We then compared their performance in resisting protein adsorption from full human serum and plasma. All five polymers can reduce protein adsorption by more than 90% compared to the unmodified gold. The ornithine-based and aspartic acid-based poly(methacrylamide) can most strongly resist protein adsorption from serum and plasma, compared to the other three. The ability of surfaces to suppress bacterial adhesion is another criterion in evaluating antifouling properties of materials. Our results show that the five polymer-grafted surfaces can significantly suppress Escherichia coli K12 adhesion to 99% compared to the bare gold surface. The zwitterionic structure of amino acids, with homogenously distributed and balanced positive and negative charges, is responsible for the outstanding antifouling properties. Considering multiple potential applications (e.g. medical devices and drug delivery) of the antifouling materials, we further systematically evaluated the cytotoxicity of both monomers and polymer nanogels for all five materials at various concentrations. Very low cytotoxicity was observed for all tested amino acid-based monomers and nanogels, which is comparable or even lower than the traditional and some newly developed antifouling materials, which might be related to the biomimetic nature of amino acids.

Extraction of domoic acid from seawater and urine using a resin based on 2-(trifluoromethyl)acrylic acid.

PubMed

Piletska, Elena V; Villoslada, Fernando Navarro; Chianella, Iva; Bossi, Alessandra; Karim, Kal; Whitcombe, Michael J; Piletsky, Sergey A; Doucette, Gregory J; Ramsdell, John S

2008-03-03

A new solid-phase extraction (SPE) matrix with high affinity for the neurotoxin domoic acid (DA) was designed and tested. A computational modelling study led to the selection of 2-(trifluoromethyl)acrylic acid (TFMAA) as a functional monomer capable of imparting affinity towards domoic acid. Polymeric adsorbents containing TFMAA were synthesised and tested in high ionic strength solutions such as urine and seawater. The TFMAA-based polymers demonstrated excellent performance in solid-phase extraction of domoic acid, retaining the toxin while salts and other interfering compounds such as aspartic and glutamic acids were removed by washing and selective elution. It was shown that the TFMAA-based polymer provided the level of purification of domoic acid from urine and seawater acceptable for its quantification by high performance liquid chromatography-mass spectrometry (HPLC-MS) and enzyme-linked immunosorbent assay (ELISA) without any additional pre-concentration and purification steps.

Efficient production of free fatty acids from ionic liquid-based acid- or enzyme-catalyzed bamboo hydrolysate.

PubMed

Mi, Le; Qin, Dandan; Cheng, Jie; Wang, Dan; Li, Sha; Wei, Xuetuan

2017-03-01

Two engineered Escherichia coli strains, DQ101 (MG1655 fadD - )/pDQTES and DQ101 (MG1655 fadD - )/pDQTESZ were constructed to investigate the free fatty acid production using ionic liquid-based acid- or enzyme-catalyzed bamboo hydrolysate as carbon source in this study. The plasmid, pDQTES, carrying an acyl-ACP thioesterase 'TesA of E. coli in pTrc99A was constructed firstly, and then (3R)-hydroxyacyl-ACP dehydratase was ligated after the TesA to give the plasmid pDQTESZ. These two strains exhibited efficient fatty acid production when glucose was used as the sole carbon source, with a final concentration of 2.45 and 3.32 g/L, respectively. The free fatty acid production of the two strains on xylose is not as efficient as that on glucose, which was 2.32 and 2.96 g/L, respectively. For mixed sugars, DQ101 (MG1655 fadD - )-based strains utilized glucose and pentose sequentially under the carbon catabolite repression (CCR) regulation. The highest total FFAs concentration from the mixed sugar culture reached 2.81 g/L by DQ101 (MG1655 fadD - )/pDQTESZ. Furthermore, when ionic liquid-based enzyme-catalyzed bamboo hydrolysate was used as the carbon source, the strain DQ101 (MG1655 fadD - )/pDQTESZ could produce 1.23 g/L FFAs with a yield of 0.13 g/g, and while it just produced 0.65 g/L free fatty acid with the ionic liquid-based acid-catalyzed bamboo hydrolysate as the feedstock. The results suggested that enzymatic catalyzed bamboo hydrolysate with ionic liquid pretreatment could serve as an efficient feedstock for free fatty acid production.

High natural antibody titers of indigenous chickens are related with increased hazard in confinement

PubMed Central

Wondmeneh, E.; Van Arendonk, J. A. M.; Van der Waaij, E. H.; Ducro, B. J.; Parmentier, H. K.

2015-01-01

Natural antibody (NAb) levels and survival rates were evaluated in 4 breeds of laying hens in Ethiopia: indigenous, improved indigenous, exotic layer, and crossbred. Titers of NAb isotypes IgG and IgM binding keyhole limpet hemocyanin (KLH) in serum were measured at 20, 26, 35, and 45 wk age. Repeated-measure ANOVA showed that IgG and IgM levels vary with time within each breed (P < 0.05). Indigenous chickens had significantly (P < 0.05) higher NAb levels at all ages. The Cox proportional hazard analysis showed increased hazard with increased levels of NAbs in the exotic layers (P < 0.05). However, the reduced hazards with increased levels of NAbs were not significant in the improved indigenous and crossbred chickens. Indigenous chickens showed increased hazard with increasing levels of NAb (P > 0.05). We concluded that not only the NAb levels but also the effect of Nabs on survival vary between indigenous and improved breeds. The results indicate that NAb levels are associated with survival in elite (improved) breeds, but are associated with increased hazard in indigenous chickens. PMID:25910906

Eligibility of Metastatic Pancreatic Cancer Patients for First-Line Palliative Intent nab-Paclitaxel Plus Gemcitabine Versus FOLFIRINOX.

PubMed

Peixoto, Renata D; Ho, Maria; Renouf, Daniel J; Lim, Howard J; Gill, Sharlene; Ruan, Jenny Y; Cheung, Winson Y

2017-10-01

The PRODIGE and MPACT trials showed superiority of FOLFIRINOX and nab-paclitaxel plus gemcitabine (NG) over gemcitabine alone, respectively. However, both had strict inclusion criteria. We sought to determine the characteristics of patients with metastatic pancreatic cancer (MPC) which inform the appropriateness of first-line chemotherapy FOLFIRINOX and NG in routine practice. Patients with MPC who initiated palliative chemotherapy with gemcitabine from 2000 to 2011 at the British Columbia Cancer Agency were identified. Clinicopathologic variables and outcomes were retrospectively collected and compared among groups. Eligibility criteria for each regimen were in accordance with the respective pivotal phase III trials. A total of 473 patients were included: 25% of the patients were eligible for FOLFIRINOX versus 45% for NG. Main reasons for FOLFIRINOX ineligibility were Eastern Cooperative Oncology Group (ECOG) performance status (PS)≥2 (56.5%), age older than 75 years (19.0%), and bilirubin>1.5× upper limit of normal (18.6%), whereas those for NG ineligibility were bilirubin > upper limit of normal (24.5%), ECOG PS≥3 (14.6%), and cardiac dysfunction (13.8%). Univariate analyses revealed that FOLFIRINOX and NG-eligible patients had longer median overall survival than their respective ineligible group (8.6 vs. 4.7 mo, P<0.001; 6.7 vs. 4.9 mo, P=0.008, respectively). After accounting for ECOG PS in the multivariate model, however, eligibility for either FOLFIRINOX or NG no longer predicted for better overall survival. The majority of patients with MPC are not candidates to either NG or FOLFIRINOX due to restrictive eligibility requirements. Specific trials addressing the unmet needs of protocol ineligible patients are warranted.

[What is the contribution of Stewart's concept in acid-base disorders analysis?].

PubMed

Quintard, H; Hubert, S; Ichai, C

2007-05-01

To explain the different approaches for interpreting acid-base disorders; to develop the Stewart model which offers some advantages for the pathophysiological understanding and the clinical interpretation of acid-base imbalances. Record of french and english references from Medline data base. The keywords were: acid-base balance, hyperchloremic acidosis, metabolic acidosis, strong ion difference, strong ion gap. Data were selected including prospective and retrospective studies, reviews, and case reports. Acid-base disorders are commonly analysed by using the traditional Henderson-Hasselbalch approach which attributes the variations in plasma pH to the modifications in plasma bicarbonates or PaCO2. However, this approach seems to be inadequate because bicarbonates and PaCO2 are completely dependent. Moreover, it does not consider the role of weak acids such as albuminate, in the determination of plasma pH value. According to the Stewart concept, plasma pH results from the degree of plasma water dissociation which is determined by 3 independent variables: 1) strong ion difference (SID) which is the difference between all the strong plasma cations and anions; 2) quantity of plasma weak acids; 3) PaCO2. Thus, metabolic acid-base disorders are always induced by a variation in SID (decreased in acidosis) or in weak acids (increased in acidosis), whereas respiratory disorders remains the consequence of a change in PaCO2. These pathophysiological considerations are important to analyse complex acid-base imbalances in critically ill patients. For example, due to a decrease in weak acids, hypoalbuminemia increases SID which may counter-balance a decrease in pH and an elevated anion gap. Thus if using only traditional tools, hypoalbuminemia may mask a metabolic acidosis, because of a normal pH and a normal anion gap. In this case, the association of metabolic acidosis and alkalosis is only expressed by respectively a decreased SID and a decreased weak acids concentration

PULSED EDDY CURRENT THICKNESS MEASUREMENT OF SELECTIVE PHASE CORROSION ON NICKEL ALUMINUM BRONZE VALVES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krause, T. W.; Harlley, D.; Babbar, V. K.

Nickel Aluminum Bronze (NAB) is a material with marine environment applications that under certain conditions can undergo selective phase corrosion (SPC). SPC involves the removal of minority elements while leaving behind a copper matrix. Pulsed eddy current (PEC) was evaluated for determination of SPC thickness on a NAB valve section with access from the surface corroded side. A primarily linear response of PEC amplitude, up to the maximum available SPC thickness of 4 mm was observed. The combination of reduced conductivity and permeability in the SPC phase relative to the base NAB was used to explain the observed sensitivity ofmore » PEC to SPC thickness variations.« less

NPIDB: Nucleic acid-Protein Interaction DataBase.

PubMed

Kirsanov, Dmitry D; Zanegina, Olga N; Aksianov, Evgeniy A; Spirin, Sergei A; Karyagina, Anna S; Alexeevski, Andrei V

2013-01-01

The Nucleic acid-Protein Interaction DataBase (http://npidb.belozersky.msu.ru/) contains information derived from structures of DNA-protein and RNA-protein complexes extracted from the Protein Data Bank (3846 complexes in October 2012). It provides a web interface and a set of tools for extracting biologically meaningful characteristics of nucleoprotein complexes. The content of the database is updated weekly. The current version of the Nucleic acid-Protein Interaction DataBase is an upgrade of the version published in 2007. The improvements include a new web interface, new tools for calculation of intermolecular interactions, a classification of SCOP families that contains DNA-binding protein domains and data on conserved water molecules on the DNA-protein interface.

Sodium butyrate attenuates high-fat diet-induced steatohepatitis in mice by improving gut microbiota and gastrointestinal barrier.

PubMed

Zhou, Da; Pan, Qin; Xin, Feng-Zhi; Zhang, Rui-Nan; He, Chong-Xin; Chen, Guang-Yu; Liu, Chang; Chen, Yuan-Wen; Fan, Jian-Gao

2017-01-07

To investigate whether gut microbiota metabolite sodium butyrate (NaB) is an effective substance for attenuating non-alcoholic fatty liver disease (NAFLD) and the internal mechanisms. Male C57BL/6J mice were divided into three groups, normal control were fed standard chow and model group were fed a high-fat diet (HFD) for 16 wk, the intervention group were fed HFD for 16 wk and treated with NaB for 8 wk. Gut microbiota from each group were detected at baseline and at 16 wk, liver histology were evaluated and gastrointestinal barrier indicator such as zonula occluden-1 (ZO-1) were detected by immunohistochemistry and realtime-PCR, further serum or liver endotoxin were determined by ELISA and inflammation- or metabolism-associated genes were quantified by real-time PCR. NaB corrected the HFD-induced gut microbiota imbalance in mice, while it considerably elevated the abundances of the beneficial bacteria Christensenellaceae , Blautia and Lactobacillus . These bacteria can produce butyric acid in what seems like a virtuous circle. And butyrate restored HFD induced intestinal mucosa damage, increased the expression of ZO-1 in small intestine, further decreased the levels of gut endotoxin in serum and liver compared with HF group. Endotoxin-associated genes such as TLR4 and Myd88, pro-inflammation genes such as MCP-1, TNF-α, IL-1, IL-2, IL-6 and IFN-γ in liver or epididymal fat were obviously downregulated after NaB intervention. Liver inflammation and fat accumulation were ameliorated, the levels of TG and cholesterol in liver were decreased after NaB intervention, NAS score was significantly decreased, metabolic indices such as FBG and HOMA-IR and liver function indicators ALT and AST were improved compared with HF group. NaB may restore the dysbiosis of gut microbiota to attenuate steatohepatitis, which is suggested to be a potential gut microbiota modulator and therapeutic substance for NAFLD.

Cooperation between Strain-Specific and Broadly Neutralizing Responses Limited Viral Escape and Prolonged the Exposure of the Broadly Neutralizing Epitope

PubMed Central

Anthony, Colin; York, Talita; Bekker, Valerie; Matten, David; Selhorst, Philippe; Ferreria, Roux-Cil; Garrett, Nigel J.; Karim, Salim S. Abdool; Morris, Lynn; Wood, Natasha T.; Moore, Penny L.

2017-01-01

ABSTRACT V3-glycan-targeting broadly neutralizing antibodies (bNAbs) are a focus of HIV-1 vaccine development. Understanding the viral dynamics that stimulate the development of these antibodies can provide insights for immunogen design. We used a deep-sequencing approach, together with neutralization phenotyping, to investigate the rate and complexity of escape from V3-glycan-directed bNAbs compared to overlapping early strain-specific neutralizing antibody (ssNAb) responses to the V3/C3 region in donor CAP177. Escape from the ssNAb response occurred rapidly via an N334-to-N332 glycan switch, which took just 7.5 weeks to reach >50% frequency. In contrast, escape from the bNAbs was mediated via multiple pathways and took longer, with escape first occurring through an increase in V1 loop length, which took 46 weeks to reach 50% frequency, followed by an N332-to-N334 reversion, which took 66 weeks. Importantly, bNAb escape was incomplete, with contemporaneous neutralization observed up to 3 years postinfection. Both the ssNAb response and the bNAb response were modulated by the presence/absence of the N332 glycan, indicating an overlap between the two epitopes. Thus, selective pressure by ssNAbs to maintain the N332 glycan may have constrained the bNAb escape pathway. This slower and incomplete viral escape resulted in prolonged exposure of the bNAb epitope, which may in turn have aided the maturation of the bNAb lineage. IMPORTANCE The development of an HIV-1 vaccine is of paramount importance, and broadly neutralizing antibodies are likely to be a key component of a protective vaccine. The V3-glycan-targeting bNAb responses are among the most promising vaccine targets, as they are commonly elicited during infection. Understanding the interplay between viral evolution and the development of these antibodies provides insights that may guide immunogen design. Our work contrasted the dynamics of the early strain-specific antibodies and the later broadly neutralizing

Molecular mechanisms of acid-base sensing by the kidney.

PubMed

Brown, Dennis; Wagner, Carsten A

2012-05-01

A major function of the kidney is to collaborate with the respiratory system to maintain systemic acid-base status within limits compatible with normal cell and organ function. It achieves this by regulating the excretion and recovery of bicarbonate (mainly in the proximal tubule) and the secretion of buffered protons (mainly in the distal tubule and collecting duct). How proximal tubular cells and distal professional proton transporting (intercalated) cells sense and respond to changes in pH, bicarbonate, and CO(2) status is a question that has intrigued many generations of renal physiologists. Over the past few years, however, some candidate molecular pH sensors have been identified, including acid/alkali-sensing receptors (GPR4, InsR-RR), kinases (Pyk2, ErbB1/2), pH-sensitive ion channels (ASICs, TASK, ROMK), and the bicarbonate-stimulated adenylyl cyclase (sAC). Some acid-sensing mechanisms in other tissues, such as CAII-PDK2L1 in taste buds, might also have similar roles to play in the kidney. Finally, the function of a variety of additional membrane channels and transporters is altered by pH variations both within and outside the cell, and the expression of several metabolic enzymes are altered by acid-base status in parts of the nephron. Thus, it is possible that a master pH sensor will never be identified. Rather, the kidney seems equipped with a battery of molecules that scan the epithelial cell environment to mount a coordinated physiologic response that maintains acid-base homeostasis. This review collates current knowledge on renal acid-base sensing in the context of a whole organ sensing and response process.

Nucleic acid aptamer-based methods for diagnosis of infections.

PubMed

Park, Ki Soo

2018-04-15

Infectious diseases are a serious global problem, which not only take an enormous human toll but also incur tremendous economic losses. In combating infectious diseases, rapid and accurate diagnostic tests are required for pathogen identification at the point of care (POC). In this review, investigations of diagnostic strategies for infectious diseases that are based on aptamers, especially nucleic acid aptamers, oligonucleotides that have high affinities and specificities toward their targets, are described. Owing to their unique features including low cost of production, easy chemical modification, high chemical stability, reproducibility, and low levels of immunogenicity and toxicity, aptamers have been widely utilized as bio-recognition elements (bio-receptors) for the development of infection diagnostic systems. We discuss nucleic acid aptamer-based methods that have been developed for diagnosis of infections using a format that organizes discussion according to the target pathogenic analytes including toxins or proteins, whole cells and nucleic acids. Also included is, a summary of recent advances made in the sensitive detection of pathogenic bacteria utilizing the isothermal nucleic acid amplification method. Lastly, a nucleic acid aptamer-based POC system is described and future directions of studies in this area are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Improving Pharmacy Students' Understanding and Long-term Retention of Acid-Base Chemistry

PubMed Central

2007-01-01

Despite repeated exposure to the principles underlying the behavior of organic acids and bases in aqueous solution, some pharmacy students remain confused about the topic of acid-base chemistry. Since a majority of organic drug molecules have acid-base character, the ability to predict their reactivity and the extent to which they will ionize in a given medium is paramount to students' understanding of essentially all aspects of drug action in vivo and in vitro. This manuscript presents a medicinal chemistry lesson in the fundamentals of acid-base chemistry that many pharmacy students have found enlightening and clarifying PMID:19503706

How Do Undergraduate Students Conceptualize Acid-Base Chemistry? Measurement of a Concept Progression

ERIC Educational Resources Information Center

Romine, William L.; Todd, Amber N.; Clark, Travis B.

2016-01-01

We developed and validated a new instrument, called "Measuring Concept progressions in Acid-Base chemistry" (MCAB) and used it to better understand the progression of undergraduate students' understandings about acid-base chemistry. Items were developed based on an existing learning progression for acid-base chemistry. We used the Rasch…

Jigsaw Cooperative Learning: Acid-Base Theories

ERIC Educational Resources Information Center

Tarhan, Leman; Sesen, Burcin Acar

2012-01-01

This study focused on investigating the effectiveness of jigsaw cooperative learning instruction on first-year undergraduates' understanding of acid-base theories. Undergraduates' opinions about jigsaw cooperative learning instruction were also investigated. The participants of this study were 38 first-year undergraduates in chemistry education…

Fermented probiotic beverages based on acid whey.

PubMed

Skryplonek, Katarzyna; Jasińska, Małgorzata

2015-01-01

Production of fermented probiotic beverages can be a good method for acid whey usage. The obtained products combine a high nutritional value of whey with health benefits claimed for probiotic bacteria. The aim of the study was to define quality properties of beverages based on fresh acid whey and milk with addition of buttermilk powder or sweet whey powder. Samples were inoculated with two strains of commercial probiotic cultures: Lactobacillus acidophilus La-5 or Bifidobacterium animalis Bb-12. After fermentation, samples were stored at refrigerated conditions. After 1, 4, 7, 14 and 21 days sensory characteristics, hardness, acetaldehyde content, titratable acidity, pH acidity and count of bacteria cells were evaluated. Throughout all storage period, the number of bacteria was higher than 8 log cfu/ml in the all samples. Beverages with La-5 strain had higher hardness and acidity, whilst samples with Bb-12 contained more acetaldehyde. Samples with buttermilk powder had better sensory properties than with sweet whey powder. Obtained products made of acid whey combined with milk and fortified with buttermilk powder or sweet whey powder, are good medium for growth and survival of examined probiotic bacteria strains. The level of bacteria was sufficient to provide health benefits to consumers.

Food composition and acid-base balance: alimentary alkali depletion and acid load in herbivores.

PubMed

Kiwull-Schöne, Heidrun; Kiwull, Peter; Manz, Friedrich; Kalhoff, Hermann

2008-02-01

Alkali-enriched diets are recommended for humans to diminish the net acid load of their usual diet. In contrast, herbivores have to deal with a high dietary alkali impact on acid-base balance. Here we explore the role of nutritional alkali in experimentally induced chronic metabolic acidosis. Data were collected from healthy male adult rabbits kept in metabolism cages to obtain 24-h urine and arterial blood samples. Randomized groups consumed rabbit diets ad libitum, providing sufficient energy but variable alkali load. One subgroup (n = 10) received high-alkali food and approximately 15 mEq/kg ammonium chloride (NH4Cl) with its drinking water for 5 d. Another group (n = 14) was fed low-alkali food for 5 d and given approximately 4 mEq/kg NH4Cl daily for the last 2 d. The wide range of alimentary acid-base load was significantly reflected by renal base excretion, but normal acid-base conditions were maintained in the arterial blood. In rabbits fed a high-alkali diet, the excreted alkaline urine (pH(u) > 8.0) typically contained a large amount of precipitated carbonate, whereas in rabbits fed a low-alkali diet, both pH(u) and precipitate decreased considerably. During high-alkali feeding, application of NH4Cl likewise decreased pH(u), but arterial pH was still maintained with no indication of metabolic acidosis. During low-alkali feeding, a comparably small amount of added NH4Cl further lowered pH(u) and was accompanied by a significant systemic metabolic acidosis. We conclude that exhausted renal base-saving function by dietary alkali depletion is a prerequisite for growing susceptibility to NH4Cl-induced chronic metabolic acidosis in the herbivore rabbit.

Biomedical research of novel biodegradable copoly(amino acid)s based on 6-aminocaproic acid and L-proline.

PubMed

Zhang, Weipeng; Shao, Jianmin

2010-08-01

The biomedical properties of novel biodegradable copoly(amino acid)s based on 6-aminocaproic acid and L-proline were analyzed in this article. The cytotoxicity of the copolymer films was tested in vitro using human embryonic kidney (HEK) 293 cells. The cell proliferation, cell cycle, cell apoptosis, and hemolysis of the polymers were also investigated. No significant cytotoxic response was detected statistically by cytotoxicity assay, and the results of cell apoptosis and cell cycle showed that there were no statistically significant differences in them. Generally, the cells spread and grew well on polymer film. Meanwhile, the extent of hemolysis on the polymers was acceptable. Evaluation of cytotoxicity by cell cycle and apoptosis as a supplementary assay is correspondingly discussed in this article. (c) 2010 Wiley Periodicals, Inc.

High natural antibody titers of indigenous chickens are related with increased hazard in confinement.

PubMed

Wondmeneh, E; Van Arendonk, J A M; Van der Waaij, E H; Ducro, B J; Parmentier, H K

2015-07-01

Natural antibody (NAb) levels and survival rates were evaluated in 4 breeds of laying hens in Ethiopia: indigenous, improved indigenous, exotic layer, and crossbred. Titers of NAb isotypes IgG and IgM binding keyhole limpet hemocyanin (KLH) in serum were measured at 20, 26, 35, and 45 wk age. Repeated-measure ANOVA showed that IgG and IgM levels vary with time within each breed (P < 0.05). Indigenous chickens had significantly (P < 0.05) higher NAb levels at all ages. The Cox proportional hazard analysis showed increased hazard with increased levels of NAbs in the exotic layers (P < 0.05). However, the reduced hazards with increased levels of NAbs were not significant in the improved indigenous and crossbred chickens. Indigenous chickens showed increased hazard with increasing levels of NAb (P > 0.05). We concluded that not only the NAb levels but also the effect of Nabs on survival vary between indigenous and improved breeds. The results indicate that NAb levels are associated with survival in elite (improved) breeds, but are associated with increased hazard in indigenous chickens. © The Author 2015. Published by Oxford University Press on behalf of Poultry Science Association.

Thai Grade 11 Students' Alternative Conceptions for Acid-Base Chemistry

ERIC Educational Resources Information Center

Artdej, Romklao; Ratanaroutai, Thasaneeya; Coll, Richard Kevin; Thongpanchang, Tienthong

2010-01-01

This study involved the development of a two-tier diagnostic instrument to assess Thai high school students' understanding of acid-base chemistry. The acid-base diagnostic test (ABDT) comprising 18 items was administered to 55 Grade 11 students in a science and mathematics programme during the second semester of the 2008 academic year. Analysis of…

Investigation of neuronal auto-antibodies in systemic lupus erythematosus patients with epilepsy.

PubMed

Karaaslan, Zerrin; Ekizoğlu, Esme; Tektürk, Pınar; Erdağ, Ece; Tüzün, Erdem; Bebek, Nerses; Gürses, Candan; Baykan, Betül

2017-01-01

Epilepsy is an important feature for neuropsychiatric involvement in systemic lupus erythematosus (SLE) with unknown mechanism. Our aim was to investigate the presence of neuronal auto-antibodies (NAbs) in neuropsychiatric SLE (NPSLE). Eighteen SLE patients (17 females, 1 male) experiencing recurrent seizures were enrolled to this study. Their clinical characteristics, EEG and MRI findings and follow-up information were evaluated from their files. Antibodies against voltage-gated potassium channel (VGKC)-complex antigens, contactin-associated protein-like 2 (CASPR-2), leucine-rich, glioma inactivated 1 (LGI1), glutamic acid decarboxylase (GAD), N-methyl-d-aspartate receptor (NMDA-R), alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptor (AMPA-R) and type B gamma aminobutyric acid receptors (GABA B -R) were screened in the sera of these patients. Moreover, indirect immunohistochemistry and immunocytochemistry tests were performed to reveal neuropil antibodies. Six out of 18 patients (33.3%) had various forms of NAbs. Among them, one patient had antibodies against GAD, one patient with hippocampal sclerosis on MRI was CASPR-2 antibody positive, whereas the remaining four patients showed hippocampal neuropil staining. We could not find a significant difference between seropositive and seronegative groups, regarding the clinical characteristics, EEG and MRI findings. This study is the first to show hippocampal neuronal staining (4/18) reflecting antibodies against unknown neuronal cell surface antigens in SLE patients with epilepsy, besides the rare occurrence of GAD and CASPR2 antibodies. Further prospective studies are needed to search for new NAbs and uncover their pathogenic role in SLE associated with epilepsy. Copyright © 2016 Elsevier B.V. All rights reserved.

Active-learning versus teacher-centered instruction for learning acids and bases

NASA Astrophysics Data System (ADS)

Acar Sesen, Burcin; Tarhan, Leman

2011-07-01

Background and purpose: Active-learning as a student-centered learning process has begun to take more interest in constructing scientific knowledge. For this reason, this study aimed to investigate the effectiveness of active-learning implementation on high-school students' understanding of 'acids and bases'. Sample The sample of this study was 45 high-school students (average age 17 years) from two different classes, which were randomly assigned to the experimental (n = 21) and control groups (n = 25), in a high school in Turkey. Design and methods A pre-test consisting of 25 items was applied to both experimental and control groups before the treatment in order to identify student prerequisite knowledge about their proficiency for learning 'acids and bases'. A one-way analysis of variance (ANOVA) was conducted to compare the pre-test scores for groups and no significant difference was found between experimental (ME = 40.14) and control groups (MC = 41.92) in terms of mean scores (F 1,43 = 2.66, p > 0.05). The experimental group was taught using an active-learning curriculum developed by the authors and the control group was taught using traditional course content based on teacher-centered instruction. After the implementation, 'Acids and Bases Achievement Test' scores were collected for both groups. Results ANOVA results showed that students' 'Acids and Bases Achievement Test' post-test scores differed significantly in terms of groups (F 1,43 = 102.53; p < 0.05). Additionally, in this study 54 misconceptions, 14 of them not reported in the literature before, were observed in the following terms: 'acid and base theories'; 'metal and non-metal oxides'; 'acid and base strengths'; 'neutralization'; 'pH and pOH'; 'hydrolysis'; 'acid-base equilibrium'; 'buffers'; 'indicators'; and 'titration'. Based on the achievement test and individual interview results, it was found that high-school students in the experimental group had fewer misconceptions and understood the

Design of cinnamaldehyde amino acid Schiff base compounds based on the quantitative structure–activity relationship

Treesearch

Hui Wang; Mingyue Jiang; Shujun Li; Chung-Yun Hse; Chunde Jin; Fangli Sun; Zhuo Li

2017-01-01

Cinnamaldehyde amino acid Schiff base (CAAS) is a new class of safe, bioactive compounds which could be developed as potential antifungal agents for fungal infections. To design new cinnamaldehyde amino acid Schiff base compounds with high bioactivity, the quantitative structure–activity relationships (QSARs) for CAAS compounds against Aspergillus niger (A. niger) and...

Syntheses and structure characterization of ten acid-base hybrid crystals based on N-containing aromatic brønsted bases and mineral acids

NASA Astrophysics Data System (ADS)

Lin, Zhihao; Jin, Shouwen; Li, Xiaoliang; Xiao, Xiao; Hu, Kaikai; Guo, Ming; Chi, Xinchen; Liu, Hui; Wang, Daqi

2017-10-01

Cocrystallization of the aromatic brønsted bases with a series of mineral acids gave a total of ten hybrid salts with the compositions: (2-methylquinoline)2: (hydrochloride acid): 3H2O [(HL1)+. (L1)·· (Cl-) · (H2O)3] (1), (6-bromobenzo[d]thiazol-2-amine): (hydrochloride acid) [(HL2)+. (Cl-)] (2), (6-bromobenzo[d]thiazol-2-amine): (nitric acid) [(HL2)+. (NO3-)] (3), (6-bromobenzo[d]thiazol-2-amine): (sulfuric acid) [(HL2)+ · (HSO4)-] (4), (6-bromobenzo[d]thiazol-2-amine): (phosphoric acid) [(HL2)+ · (H2PO4)-] (5), (5,7-dimethyl-1,8-naphthyridine-2-amine): (hydrochloride acid): 3H2O [(HL3)+ · (Cl-) (H2O)3] (6), (5,7-dimethyl-1,8-naphthyridine-2-amine): (hydrobromic acid): CH3OH [(HL3)+ · (Br)- · CH3OH] (7), (5,7-dimethyl-1,8-naphthyridine-2-amine): (sulfuric acid): H2O [(HL3)+ · (HSO4)- · H2O] (8), (2-aminophenol): (phosphoric acid) [(HL4)+ · (H2PO4)-] (9), and (2-amino-4-chlorophenol): (phosphoric acid) [(HL5)+ · (H2PO4)-] (10). The ten salts have been characterized by X-ray diffraction analysis, IR, and elemental analysis, and the melting points of all the salts were also reported. And their structural and supramolecular aspects are fully analyzed. The result reveals that among the ten investigated crystals the ring N of the heterocycle or the NH2 in the aminophenol are protonated when the acids are deprotonated, and the crystal packing is interpreted in terms of the strong charge-assisted classical hydrogen bonds between the NH+/NH3+ and deprotonated acidic groups. Further analysis of the crystal packing of the salts indicated that a different family of additional CHsbnd O, CHsbnd Cl, CH3sbnd N, CH3sbnd O, CHsbnd Br, CH3sbnd Br, Brsbnd Cl, Clsbnd S, Osbnd S, Osbnd O, Brsbnd S, Hsbnd H, and π-π associations contribute to the stabilization and expansion of the total high-dimensional frameworks. For the coexistence of the various weak nonbonding interactions these structures adopted homo or hetero supramolecular synthons or both. Some classical

Reliability of Pseudotyped Influenza Viral Particles in Neutralizing Antibody Detection

PubMed Central

Yang, Jinghui; Li, Weidong; Long, Yunfeng; Song, Shaohui; Liu, Jing; Zhang, Xinwen; Wang, Xiaoguang; Jiang, Shude; Liao, Guoyang

2014-01-01

Background Current influenza control strategies require an active surveillance system. Pseudotyped viral particles (pp) together with the evaluation of pre-existing immunity in a population might satisfy this requirement. However, the reliability of using pp in neutralizing antibody (nAb) detection are undefined. Methodology/Principal Findings Pseudotyped particles of A(H1N1)pmd09 (A/California/7/2009) and HPAI H5N1 (A/Anhui/1/2005), as well as their reassortants, were generated. The reliability of using these pp in nAb detection were compared concurrently with the corresponding viruses by a hemagglutination inhibition test, as well as ELISA-, cytopathic effect-, and fluorescence-based microneutralization assays. In the qualitative detection on nAbs, the pp and their corresponding viruses were in complete agreement, with an R2 value equal to or near 1 in two different populations. In the quantitative detection on nAbs, although the geometric mean titers (95% confidence interval) differed between the pp and viruses, no significant difference was observed. Furthermore, humoral immunity against the reassortants was evaluated; our results indicated strong consistency between the nAbs against reassortant pp and those against naïve pp harboring the same hemagglutinin. Conclusion/Significance The pp displayed high reliability in influenza virus nAb detection. The use of reassortant pp is a safe and convenient strategy for characterizing emerging influenza viruses and surveying the disease burden. PMID:25436460

Amino acid-based dithiazines: synthesis and photofragmentation of their benzaldehyde adducts.

PubMed

Kurchan, Alexei N; Kutateladze, Andrei G

2002-11-14

Alpha-amino acids and GABA are functionalized with dithiazine rings via reaction with sodium hydrosulfide in aqueous formaldehyde. The resulting dithiazines are lithiated at -78 degrees C and reacted with benzaldehyde furnishing amino acid-based 2,5-bis-substituted dithiazines. These adducts undergo externally sensitized photofragmentation with quantum efficiency comparable to that of the parent dithiane adducts, thus offering a novel approach to amino acid-based photolabile tethers. [reaction: see text

High Performance Fatty Acid-Based Vinyl Ester Resin for Liquid Molding

DTIC Science & Technology

2007-07-01

High Performance Fatty Acid -Based Vinyl Ester Resin for Liquid Molding by Xing Geng, John J. La Scala, James M. Sands, and Giuseppe R...it to the originator. Army Research Laboratory Aberdeen Proving Ground, MD 21005-5069 ARL-RP-184 July 2007 High Performance Fatty Acid ...CONTRACT NUMBER 5b. GRANT NUMBER 4. TITLE AND SUBTITLE High Performance Fatty Acid -Based Vinyl Ester Resin for Liquid Molding 5c. PROGRAM

Strong ion calculator--a practical bedside application of modern quantitative acid-base physiology.

PubMed

Lloyd, P

2004-12-01

To review acid-base balance by considering the physical effects of ions in solution and describe the use of a calculator to derive the strong ion difference and Atot and strong ion gap. A review of articles reporting on the use of strong ion difference and Atot in the interpretation of acid base balance. Tremendous progress has been made in the last decade in our understanding of acid-base physiology. We now have a quantitative understanding of the mechanisms underlying the acidity of an aqueous solution. We can now predict the acidity given information about the concentration of the various ion-forming species within it. We can predict changes in acid-base status caused by disturbance of these factors, and finally, we can detect unmeasured anions with greater sensitivity than was previously possible with the anion gap, using either arterial or venous blood sampling. Acid-base interpretation has ceased to be an intuitive and arcane art. Much of it is now an exact computation that can be automated and incorporated into an online hospital laboratory information system. All diseases and all therapies can affect a patient's acid-base status only through the final common pathway of one or more of the three independent factors. With Constable's equations we can now accurately predict the acidity of plasma. When there is a discrepancy between the observed and predicted acidity we can deduce the net concentration of unmeasured ions to account for the difference.

In vitro fruiting of Armillaria species.

Treesearch

Jimmy L. Reaves; Michael. McWilliams

1991-01-01

Thirty-three different isolates of various Armillaria species were grown on sterilized orange slices under a controlled temperature and light regime. Nine isolates of A. ostoyae (North American Biological Species I, NABS I), three of NABS VII, one of NABS IX, one of NABS X, and two unidentified isolates formed basidiomes. Most...

A Comparison of Different Teaching Designs of "Acids and Bases" Subject

ERIC Educational Resources Information Center

Ültay, Neslihan; Çalik, Muammer

2016-01-01

Inability to link the acid-base concepts with daily life phenomena (as contexts) highlights the need for further research on the context-based acid-base chemistry. In this vein, the aim of this study is to investigate the effects of different teaching designs (REACT strategy, 5Es learning model and traditional (existing) instruction) relevant with…

Conformational Behaviour of Azasugars Based on Mannuronic Acid.

PubMed

van Rijssel, Erwin R; Janssen, Antonius P A; Males, Alexandra; Davies, Gideon J; van der Marel, Gijsbert A; Overkleeft, Herman S; Codée, Jeroen D C

2017-07-04

A set of mannuronic-acid-based iminosugars, consisting of the C-5-carboxylic acid, methyl ester and amide analogues of 1deoxymannorjirimicin (DMJ), was synthesised and their pH-dependent conformational behaviour was studied. Under acidic conditions the methyl ester and the carboxylic acid adopted an "inverted" 1 C 4 chair conformation as opposed to the "normal" 4 C 1 chair at basic pH. This conformational change is explained in terms of the stereoelectronic effects of the ring substituents and it parallels the behaviour of the mannuronic acid ester oxocarbenium ion. Because of this solution-phase behaviour, the mannuronic acid ester azasugar was examined as an inhibitor for a Caulobacter GH47 mannosidase that hydrolyses its substrates by way of a reaction itinerary that proceeds through a 3 H 4 transition state. No binding was observed for the mannuronic acid ester azasugar, but sub-atomic resolution data were obtained for the DMJ⋅CkGH47 complex, showing two conformations- 3 S 1 and 1 C 4 -for the DMJ inhibitor. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Characteristics of weak base-induced vacuoles formed around individual acidic organelles.

PubMed

Hiruma, Hiromi; Kawakami, Tadashi

2011-01-01

We have previously found that the weak base 4-aminopyridine induces Brownian motion of acidic organelles around which vacuoles are formed, causing organelle traffic disorder in neurons. Our present study investigated the characteristics of vacuoles induced by weak bases (NH(4)Cl, aminopyridines, and chloroquine) using mouse cells. Individual vacuoles included acidic organelles identified by fluorescent protein expression. Mitochondria and actin filaments were extruded outside the vacuoles, composing the vacuole rim. Staining with amine-reactive fluorescence showed no protein/amino acid content in vacuoles. Thus, serous vacuolar contents are probably partitioned by viscous cytosol, other organelles, and cytoskeletons, but not membrane. The weak base (chloroquine) was immunochemically detected in intravacuolar organelles, but not in vacuoles. Early vacuolization was reversible, but long-term vacuolization caused cell death. The vacuolization and cell death were blocked by the vacuolar H(+)-ATPase inhibitor and Cl--free medium. Staining with LysoTracker or LysoSensor indicated that intravacuolar organelles were strongly acidic and vacuoles were slightly acidic. This suggests that vacuolization is caused by accumulation of weak base and H(+) in acidic organelles, driven by vacuolar H(+)-ATPase associated with Cl(-) entering, and probably by subsequent extrusion of H(+) and water from organelles to the surrounding cytoplasm.

Low-affinity FcγR interactions can decide the fate of novel human IgG-sensitised red blood cells and platelets

PubMed Central

Armour, Kathryn L; Smith, Cheryl S; Turner, Craig P; Kirton, Christopher M; Wilkes, Anthony M; Hadley, Andrew G; Ghevaert, Cedric; Williamson, Lorna M; Clark, Michael R

2014-01-01

G1Δnab is a mutant human IgG1 constant region with a lower ability to interact with FcγR than the natural IgG constant regions. Radiolabelled RBCs and platelets sensitised with specific G1Δnab Abs were cleared more slowly from human circulation than IgG1-sensitised counterparts. However, non-destructive splenic retention of G1Δnab-coated RBCs required investigation and plasma radioactivities now suggest this also occurred for platelets sensitised with an IgG1/G1Δnab mixture. In vitro assays with human cells showed that G1Δnab-sensitised RBCs did not cause FcγRI-mediated monocyte activation, FcγRIIIa-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) or macrophage phagocytosis although they did adhere to macrophages. Thus, FcγRII was implicated in the adhesion despite the Δnab mutation reducing the already low-affinity binding to this receptor class. Additional contacts via P-selectin enhance the interaction of sensitised platelets with monocytes and this system provided evidence of FcγRII-dependent activation by G1Δnab. These results emphasise the physiological relevance of low-affinity interactions: It appears that FcγRII interactions of G1Δnab allowed splenic retention of G1Δnab-coated RBCs with inhibitory FcγRIIb binding preventing RBC destruction and that FcγRIIb engagement by G1Δnab on IgG1/G1Δnab-sensitised platelets overcame activation by IgG1. Considering therapeutic blocking Abs, G1Δnab offers lower FcγR binding and a greater bias towards inhibition than IgG2 and IgG4 constant regions. PMID:24285214

Low-affinity FcγR interactions can decide the fate of novel human IgG-sensitised red blood cells and platelets.

PubMed

Armour, Kathryn L; Smith, Cheryl S; Turner, Craig P; Kirton, Christopher M; Wilkes, Anthony M; Hadley, Andrew G; Ghevaert, Cedric; Williamson, Lorna M; Clark, Michael R

2014-03-01

G1Δnab is a mutant human IgG1 constant region with a lower ability to interact with FcγR than the natural IgG constant regions. Radiolabelled RBCs and platelets sensitised with specific G1Δnab Abs were cleared more slowly from human circulation than IgG1-sensitised counterparts. However, non-destructive splenic retention of G1Δnab-coated RBCs required investigation and plasma radioactivities now suggest this also occurred for platelets sensitised with an IgG1/G1Δnab mixture. In vitro assays with human cells showed that G1Δnab-sensitised RBCs did not cause FcγRI-mediated monocyte activation, FcγRIIIa-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) or macrophage phagocytosis although they did adhere to macrophages. Thus, FcγRII was implicated in the adhesion despite the Δnab mutation reducing the already low-affinity binding to this receptor class. Additional contacts via P-selectin enhance the interaction of sensitised platelets with monocytes and this system provided evidence of FcγRII-dependent activation by G1Δnab. These results emphasise the physiological relevance of low-affinity interactions: It appears that FcγRII interactions of G1Δnab allowed splenic retention of G1Δnab-coated RBCs with inhibitory FcγRIIb binding preventing RBC destruction and that FcγRIIb engagement by G1Δnab on IgG1/G1Δnab-sensitised platelets overcame activation by IgG1. Considering therapeutic blocking Abs, G1Δnab offers lower FcγR binding and a greater bias towards inhibition than IgG2 and IgG4 constant regions. © 2013 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Surface acid-base behaviors of Chinese loess.

PubMed

Chu, Zhaosheng; Liu, Wenxin; Tang, Hongxiao; Qian, Tianwei; Li, Shushen; Li, Zhentang; Wu, Guibin

2002-08-15

Acid-base titration was applied to investigate the surface acid-base properties of a Chinese loess sample at different ionic strengths. The acidimetric supernatant was regarded as the system blank of titration to correct the influence of particle dissolution on the estimation of proton consumption. The titration behavior of the system blank could be described by the hydrolysis of Al3+ and Si(OH)4 in aqueous solution as well as the production of hydroxyaluminosilicates. The formation of Al-Si species on homogeneous surface sites by hydrous aluminum and silicic acid, released from solid substrate during the acidic titration, was considered in the model description of the back-titration procedure. A surface reaction model was suggested as follows: >SOH<-->SO(-)+H+, pK(a)(int)=3.48-3.98;>SOH+Al(3+)+H4SiO4<-->SOAl(OSi(OH)3(+)+2H+, pK(SC)=3.48-4.04. Two simple surface complexation models accounted for the interfacial structure, i.e., the constant capacitance model (CCM) and the diffuse layer model (DLM), and gave a satisfactory description of the experimental data. Considering the effect of ionic strength on the electrostatic profile at the solid-aqueous interface, the DLM was appropriate at the low concentrations (0.01 and 0.005 mol/L) of background electrolyte (NaNO3 in this study), while the CCM was preferable in the case of high ionic strength (0.1 mol/L).

Controlling on-demand gastric acidity in obese subjects: a randomized, controlled trial comparing a single dose of 20 mg rabeprazole and 20 mg omeprazole

PubMed Central

2014-01-01

Background Obesity is associated with a risk of gastroesophageal reflux disease. The pharmacodynamic efficacy of proton pump inhibitors has not been specifically evaluated in obese subjects. The aim of this study was to compare the antisecretory response to a single oral dose of 20 mg rabeprazole, 20 mg omeprazole and placebo in obese subjects. Methods Gastric pH was monitored for 24 hours on three separate occasions in eighteen H. pylori-negative, asymptomatic obese subjects. Subjects were given omeprazole, rabeprazole or placebo in a randomized order and in a double-blind fashion. The main analysis criterion was 24-h percent of time post dose with intragastric pH above 3; secondary criteria were percentage of time above pH 4, median pH, [H+] concentrations and nocturnal acid breakthrough (NAB). Results were analyzed using linear mixed models and Wilks test comparing variances. Results 24-h median [IQ] percentages of time with gastric pH above 3 and 4 were higher with rabeprazole than omeprazole (46 [37–55] vs. 30 [15–55] %, 9 [5-11] % for placebo) but the differences did not reach statistical significance (p = 0.11 and 0.24, respectively). Median acid concentrations were significantly lower with rabeprazole than with omeprazole and placebo (22 [14–53] vs. 54 [19–130] and 95 [73–170] mmoles/l, p < 0.01) for all periods. The number of NAB was significantly lower with rabeprazole than with omeprazole (median 1 [1,2] vs. 2 [1-3], p = 0.04). Variances of 24-h data (pH above 3 and 4, median pH, [H+] concentrations) were significantly lower with rabeprazole than with omeprazole (p < 0.0001). Conclusions In asymptomatic obese subjects the gastric antisecretory response to a single dose of rabeprazole and omeprazole was strong and not significantly different between drugs despite a significantly more homogeneous response with rabeprazole. Trial registration ClinicalTrial.gov: NCT01136317 PMID:25027286

Ubiquity and Diversity of Heterotrophic Bacterial nasA Genes in Diverse Marine Environments

PubMed Central

Jiang, Xuexia; Dang, Hongyue; Jiao, Nianzhi

2015-01-01

Nitrate uptake by heterotrophic bacteria plays an important role in marine N cycling. However, few studies have investigated the diversity of environmental nitrate assimilating bacteria (NAB). In this study, the diversity and biogeographical distribution of NAB in several global oceans and particularly in the western Pacific marginal seas were investigated using both cultivation and culture-independent molecular approaches. Phylogenetic analyses based on 16S rRNA and nasA (encoding the large subunit of the assimilatory nitrate reductase) gene sequences indicated that the cultivable NAB in South China Sea belonged to the α-Proteobacteria, γ-Proteobacteria and CFB (Cytophaga-Flavobacteria-Bacteroides) bacterial groups. In all the environmental samples of the present study, α-Proteobacteria, γ-Proteobacteria and Bacteroidetes were found to be the dominant nasA-harboring bacteria. Almost all of the α-Proteobacteria OTUs were classified into three Roseobacter-like groups (I to III). Clone library analysis revealed previously underestimated nasA diversity; e.g. the nasA gene sequences affiliated with β-Proteobacteria, ε-Proteobacteria and Lentisphaerae were observed in the field investigation for the first time, to the best of our knowledge. The geographical and vertical distributions of seawater nasA-harboring bacteria indicated that NAB were highly diverse and ubiquitously distributed in the studied marginal seas and world oceans. Niche adaptation and separation and/or limited dispersal might mediate the NAB composition and community structure in different water bodies. In the shallow-water Kueishantao hydrothermal vent environment, chemolithoautotrophic sulfur-oxidizing bacteria were the primary NAB, indicating a unique nitrate-assimilating community in this extreme environment. In the coastal water of the East China Sea, the relative abundance of Alteromonas and Roseobacter-like nasA gene sequences responded closely to algal blooms, indicating that NAB may be

Analysis of neutralizing antibodies to therapeutic interferon-beta in multiple sclerosis patients: a comparison of three methods in a large Australasian cohort.

PubMed

McKay, Fiona; Schibeci, Stephen; Heard, Robert; Stewart, Graeme; Booth, David

2006-03-20

Persistent high-titre neutralizing antibodies (NAB) to therapeutic interferon-beta(IFNbeta)in multiple sclerosis patients reduce therapeutic efficacy. Difficulties in standardization of cell-based bioactivity assays have hindered interlaboratory comparison of NAB titres and the determination of a clinically relevant definition of seropositivity. We determined NAB status in Australasian multiple sclerosis patients receiving IFNbetausing both the antiviral cytopathic effect (CPE) assay (n = 227) and the more specific ELISA for the type I interferon-inducible MxA protein (n = 350). While the log(10) titres determined in the two assays were highly correlated (p < 0.0001; r = 0.967) with similar distributions, the MxA assay was more sensitive, detecting lower concentrations of NAB than the CPE assay. The range of titres determined in the CPE assay was 10 to >7290; and 9 to 53,700 in the MxA assay, with ranked titre distribution highlighting the arbitrary nature of currently accepted definitions of NAB seropositivity. Bioactivity of injected IFNbetawas significantly reduced in NAB-positive patients (p = 0.006; NAB MxA titres = 184 to 5340) compared to NAB-negative patients as assessed ex vivo using real-time RT-PCR analysis of MxA gene induction. The range of MxA mRNA levels in healthy controls was remarkably consistent with previously published results, regardless of the assay standardization method [Gilli, F., Sala, A., Marnetto, F., Lindberg, R.L., Leppert, D. and Bertolotto, A. (2003) Comparison of IFNbeta bioavailability evaluations by MxA mRNA using two independent quantification methods. Abstract, ECTRIMS Meeting, Milan, Italy; Pachner, A., Narayan, K., Price, N., Hurd, M. and Dail, D. (2003a) MxA Gene Expression Analysis as an Interferon-beta Bioactivity Measurement in Patients with Multiple Sclerosis and the Identification of Antibody-Mediated Decreased Bioactivity. Mol. Diagn. 7, 17-25]. Assessment of IFNbetaresponse ex vivo accounts for both circulating

Fabricating Superior NiAl Bronze Components through Wire Arc Additive Manufacturing.

PubMed

Ding, Donghong; Pan, Zengxi; van Duin, Stephen; Li, Huijun; Shen, Chen

2016-08-03

Cast nickel aluminum bronze (NAB) alloy is widely used for large engineering components in marine applications due to its excellent mechanical properties and corrosion resistance. Casting porosity, as well as coarse microstructure, however, are accompanied by a decrease in mechanical properties of cast NAB components. Although heat treatment, friction stir processing, and fusion welding were implemented to eliminate porosity, improve mechanical properties, and refine the microstructure of as-cast metal, their applications are limited to either surface modification or component repair. Instead of traditional casting techniques, this study focuses on developing NAB components using recently expanded wire arc additive manufacturing (WAAM). Consumable welding wire is melted and deposited layer-by-layer on substrates producing near-net shaped NAB components. Additively-manufactured NAB components without post-processing are fully dense, and exhibit fine microstructure, as well as comparable mechanical properties, to as-cast NAB alloy. The effects of heat input from the welding process and post-weld-heat-treatment (PWHT) are shown to give uniform NAB alloys with superior mechanical properties revealing potential marine applications of the WAAM technique in NAB production.

Fabricating Superior NiAl Bronze Components through Wire Arc Additive Manufacturing

PubMed Central

Ding, Donghong; Pan, Zengxi; van Duin, Stephen; Li, Huijun; Shen, Chen

2016-01-01

Cast nickel aluminum bronze (NAB) alloy is widely used for large engineering components in marine applications due to its excellent mechanical properties and corrosion resistance. Casting porosity, as well as coarse microstructure, however, are accompanied by a decrease in mechanical properties of cast NAB components. Although heat treatment, friction stir processing, and fusion welding were implemented to eliminate porosity, improve mechanical properties, and refine the microstructure of as-cast metal, their applications are limited to either surface modification or component repair. Instead of traditional casting techniques, this study focuses on developing NAB components using recently expanded wire arc additive manufacturing (WAAM). Consumable welding wire is melted and deposited layer-by-layer on substrates producing near-net shaped NAB components. Additively-manufactured NAB components without post-processing are fully dense, and exhibit fine microstructure, as well as comparable mechanical properties, to as-cast NAB alloy. The effects of heat input from the welding process and post-weld-heat-treatment (PWHT) are shown to give uniform NAB alloys with superior mechanical properties revealing potential marine applications of the WAAM technique in NAB production. PMID:28773774

Linear Titration Curves of Acids and Bases.

PubMed

Joseph, N R

1959-05-29

The Henderson-Hasselbalch equation, by a simple transformation, becomes pH - pK = pA - pB, where pA and pB are the negative logarithms of acid and base concentrations. Sigmoid titration curves then reduce to straight lines; titration curves of polyelectrolytes, to families of straight lines. The method is applied to the titration of the dipeptide glycyl aminotricarballylic acid, with four titrable groups. Results are expressed as Cartesian and d'Ocagne nomograms. The latter is of a general form applicable to polyelectrolytes of any degree of complexity.

Acid-Base Disorders--A Computer Simulation.

ERIC Educational Resources Information Center

Maude, David L.

1985-01-01

Describes and lists a program for Apple Pascal Version 1.1 which investigates the behavior of the bicarbonate-carbon dioxide buffer system in acid-base disorders. Designed specifically for the preclinical medical student, the program has proven easy to use and enables students to use blood gas parameters to arrive at diagnoses. (DH)

[Acid-base equilibrium and the brain].

PubMed

Rabary, O; Boussofara, M; Grimaud, D

1994-01-01

In physiological conditions, the regulation of acid-base balance in brain maintains a noteworthy stability of cerebral pH. During systemic metabolic acid-base imbalances cerebral pH is well controlled as the blood/brain barrier is slowly and poorly permeable to electrolytes (HCO3- and H+). Cerebral pH is regulated by a modulation of the respiratory drive, triggered by the early alterations of interstitial fluid pH, close to medullary chemoreceptors. As blood/brain barrier is highly permeable to Co2, CSF pH is corrected in a few hours, even in case of severe metabolic acidosis and alkalosis. Conversely, during ventilatory acidosis and alkalosis the cerebral pH varies in the same direction and in the same range than blood pH. Therefore, the brain is better protected against metabolic than ventilatory acid-base imbalances. Ventilatory acidosis and alkalosis are able to impair cerebral blood flow and brain activity through interstitial pH alterations. During respiratory acidosis, [HCO3-] increases in extracellular fluids to control cerebral pH by two main ways: a carbonic anhydrase activation at the blood/brain and blood/CSF barriers level and an increase in chloride shift in glial cells (HCO3- exchanged for Cl-). During respiratory alkalosis, [HCO3-] decreases in extracellular fluids by the opposite changes in HCO3- transport and by an increase in lactic acid synthesis by cerebral cells. The treatment of metabolic acidosis with bicarbonates may induce a cerebral acidosis and worsen a cerebral oedema during ketoacidosis. Moderate hypocapnia carried out to treat intracranial hypertension is mainly effective when cerebral blood flow is high and vascular CO2 reactivity maintained. Hypocapnia may restore an altered cerebral blood flow autoregulation. Instrumental hypocapnia requires a control of cerebral perfusion pressure and cerebral arteriovenous difference for oxygen, to select patients for whom this kind of treatment may be of benefit, to choose the optimal level of

Arenavirus Glycan Shield Promotes Neutralizing Antibody Evasion and Protracted Infection

PubMed Central

Malinge, Pauline; Magistrelli, Giovanni; Fischer, Nicolas; Sahin, Mehmet; Bergthaler, Andreas; Igonet, Sebastien; ter Meulen, Jan; Rigo, Dorothée; Meda, Paolo; Rabah, Nadia; Coutard, Bruno; Bowden, Thomas A.; Lambert, Paul-Henri; Siegrist, Claire-Anne; Pinschewer, Daniel D.

2015-01-01

Arenaviruses such as Lassa virus (LASV) can cause severe hemorrhagic fever in humans. As a major impediment to vaccine development, delayed and weak neutralizing antibody (nAb) responses represent a unifying characteristic of both natural infection and all vaccine candidates tested to date. To investigate the mechanisms underlying arenavirus nAb evasion we engineered several arenavirus envelope-chimeric viruses and glycan-deficient variants thereof. We performed neutralization tests with sera from experimentally infected mice and from LASV-convalescent human patients. NAb response kinetics in mice correlated inversely with the N-linked glycan density in the arenavirus envelope protein’s globular head. Additionally and most intriguingly, infection with fully glycosylated viruses elicited antibodies, which neutralized predominantly their glycan-deficient variants, both in mice and humans. Binding studies with monoclonal antibodies indicated that envelope glycans reduced nAb on-rate, occupancy and thereby counteracted virus neutralization. In infected mice, the envelope glycan shield promoted protracted viral infection by preventing its timely elimination by the ensuing antibody response. Thus, arenavirus envelope glycosylation impairs the protective efficacy rather than the induction of nAbs, and thereby prevents efficient antibody-mediated virus control. This immune evasion mechanism imposes limitations on antibody-based vaccination and convalescent serum therapy. PMID:26587982

Neutralization of Virus Infectivity by Antibodies: Old Problems in New Perspectives

PubMed Central

Klasse, P. J.

2016-01-01

Neutralizing antibodies (NAbs) can be both sufficient and necessary for protection against viral infections, although they sometimes act in concert with cellular immunity. Successful vaccines against viruses induce NAbs but vaccine candidates against some major viral pathogens, including HIV-1, have failed to induce potent and effective such responses. Theories of how antibodies neutralize virus infectivity have been formulated and experimentally tested since the 1930s; and controversies about the mechanistic and quantitative bases for neutralization have continually arisen. Soluble versions of native oligomeric viral proteins that mimic the functional targets of neutralizing antibodies now allow the measurement of the relevant affinities of NAbs. Thereby the neutralizing occupancies on virions can be estimated and related to the potency of the NAbs. Furthermore, the kinetics and stoichiometry of NAb binding can be compared with neutralizing efficacy. Recently, the fundamental discovery that the intracellular factor TRIM21 determines the degree of neutralization of adenovirus has provided new mechanistic and quantitative insights. Since TRIM21 resides in the cytoplasm, it would not affect the neutralization of enveloped viruses, but its range of activity against naked viruses will be important to uncover. These developments bring together the old problems of virus neutralization—mechanism, stoichiometry, kinetics, and efficacy—from surprising new angles. PMID:27099867

Acid base activity of live bacteria: Implications for quantifying cell wall charge

NASA Astrophysics Data System (ADS)

Claessens, Jacqueline; van Lith, Yvonne; Laverman, Anniet M.; Van Cappellen, Philippe

2006-01-01

To distinguish the buffering capacity associated with functional groups in the cell wall from that resulting from metabolic processes, base or acid consumption by live and dead cells of the Gram-negative bacterium Shewanella putrefaciens was measured in a pH stat system. Live cells exhibited fast consumption of acid (pH 4) or base (pH 7, 8, 9, and 10) during the first few minutes of the experiments. At pH 5.5, no acid or base was required to maintain the initial pH constant. The initial amounts of acid or base consumed by the live cells at pH 4, 8, and 10 were of comparable magnitudes as those neutralized at the same pHs by intact cells killed by exposure to gamma radiation or ethanol. Cells disrupted in a French press required higher amounts of acid or base, due to additional buffering by intracellular constituents. At pH 4, acid neutralization by suspensions of live cells stopped after 50 min, because of loss of viability. In contrast, under neutral and alkaline conditions, base consumption continued for the entire duration of the experiments (5 h). This long-term base neutralization was, at least partly, due to active respiration by the cells, as indicated by the build-up of succinate in solution. Qualitatively, the acid-base activity of live cells of the Gram-positive bacterium Bacillus subtilis resembled that of S. putrefaciens. The pH-dependent charging of ionizable functional groups in the cell walls of the live bacteria was estimated from the initial amounts of acid or base consumed in the pH stat experiments. From pH 4 to 10, the cell wall charge increased from near-zero values to about -4 × 10 -16 mol cell -1 and -6.5 × 10 -16 mol cell -1 for S. putrefaciens and B. subtilis, respectively. The similar cell wall charging of the two bacterial strains is consistent with the inferred low contribution of lipopolysaccharides to the buffering capacity of the Gram-negative cell wall (of the order of 10%).

The activation of the TLR2/p38 pathway by sodium butyrate in bovine mammary epithelial cells is involved in the reduction of Staphylococcus aureus internalization.

PubMed

Alva-Murillo, Nayeli; Medina-Estrada, Ivan; Báez-Magaña, Marisol; Ochoa-Zarzosa, Alejandra; López-Meza, Joel E

2015-12-01

Staphylococcus aureus is an etiological agent of human and animal diseases, and it is able to internalize into non-professional phagocytic cells (i.e. bovine mammary epithelial cells, bMECs), which is an event that is related to chronic and recurrent infections. bMECs contribute to host innate immune responses (IIR) through TLR pathogen recognition, whereby TLR2 is the most relevant for S. aureus. In a previous report, we showed that sodium butyrate (NaB, 0.5mM), which is a short chain fatty acid (SCFA), reduced S. aureus internalization into bMECs by modulating their IIR. However, the molecular mechanism of this process has not been described, which was the aim of this study. The results showed that the TLR2 membrane abundance (MA) and mRNA expression were induced by 0.5mM NaB ∼1.6-fold and ∼1.7-fold, respectively. Additionally, 0.5mM NaB induced p38 phosphorylation, but not JNK1/2 or ERK1/2 phosphorylation in bMECs, which reached the baseline when the bMECs were S. aureus-challenged. Additionally, bMECs that were treated with 0.5mM NaB (24h) showed activation of 8 transcriptional factors (AP-1, E2F-1, FAST-1, MEF-1, EGR, PPAR, ER and CBF), which were partially reverted when the bMECs were S. aureus-challenged. Additionally, 0.5mM NaB (24h) up-regulated mRNA expression of the antimicrobial peptides, TAP (∼4.8-fold), BNBD5 (∼3.2-fold) and BNBD10 (∼2.6-fold). Notably, NaB-treated and S. aureus-challenged bMECs increased the mRNA expression of all of the antimicrobial peptides that were evaluated, and this was evident for LAP and BNBD5. In the NaB-treated bMECs, we did not detect significant expression changes for IL-1β and IL-6 and only TNF-α, IL-10 and IL-8 were induced. Interestingly, the NaB-treated and S. aureus-challenged bMECs maintained the anti-inflammatory response that was induced by this SCFA. In conclusion, our results suggest that 0.5mM NaB activates bMECs via TLR2/p38, which leads to improved antimicrobial defense before/after pathogen

An Olfactory Indicator for Acid-Base Titrations.

ERIC Educational Resources Information Center

Flair, Mark N.; Setzer, William N.

1990-01-01

The use of an olfactory acid-base indicator in titrations for visually impaired students is discussed. Potential olfactory indicators include eugenol, thymol, vanillin, and thiophenol. Titrations performed with each indicator with eugenol proved to be successful. (KR)

HIV Neutralizing Antibodies Induced by Native-like Envelope Trimers

PubMed Central

Sanders, Rogier W.; van Gils, Marit J.; Derking, Ronald; Sok, Devin; Ketas, Thomas J.; Burger, Judith A.; Ozorowski, Gabriel; Cupo, Albert; Simonich, Cassandra; Goo, Leslie; Arendt, Heather; Kim, Helen J.; Lee, Jeong Hyun; Pugach, Pavel; Williams, Melissa; Debnath, Gargi; Moldt, Brian; van Breemen, Mariëlle J.; Isik, Gözde; Medina-Ramírez, Max; Back, Jaap Willem; Koff, Wayne; Julien, Jean-Philippe; Rakasz, Eva G.; Seaman, Michael S.; Guttman, Miklos; Lee, Kelly K.; Klasse, Per Johan; LaBranche, Celia; Schief, William R.; Wilson, Ian A.; Overbaugh, Julie; Burton, Dennis R.; Ward, Andrew B.; Montefiori, David C.; Dean, Hansi; Moore, John P.

2015-01-01

A challenge for HIV-1 immunogen design is inducing neutralizing antibodies (NAbs) against neutralization-resistant (Tier-2) viruses that dominate human transmissions. We show that a soluble recombinant HIV-1 envelope glycoprotein trimer that adopts a native conformation (BG505 SOSIP.664) induced NAbs potently against the sequence-matched Tier-2 virus in rabbits and similar but weaker responses in macaques. The trimer also consistently induced cross-reactive NAbs against more sensitive (Tier-1) viruses. Tier-2 NAbs recognized conformational epitopes that differed between animals and in some cases overlapped with those recognized by broadly neutralizing antibodies (bNAbs), whereas Tier-1 responses targeted linear V3 epitopes. A second trimer, B41 SOSIP.664, also induced a strong autologous Tier-2 NAb response in rabbits. Thus, native-like trimers represent a promising starting point for developing HIV-1 vaccines aimed at inducing bNAbs. PMID:26089353

Biodegradation and Osteosarcoma Cell Cultivation on Poly(aspartic acid) Based Hydrogels.

PubMed

Juriga, Dávid; Nagy, Krisztina; Jedlovszky-Hajdú, Angéla; Perczel-Kovách, Katalin; Chen, Yong Mei; Varga, Gábor; Zrínyi, Miklós

2016-09-14

Development of novel biodegradable and biocompatible scaffold materials with optimal characteristics is important for both preclinical and clinical applications. The aim of the present study was to analyze the biodegradability of poly(aspartic acid)-based hydrogels, and to test their usability as scaffolds for MG-63 osteoblast-like cells. Poly(aspartic acid) was fabricated from poly(succinimide) and hydrogels were prepared using natural amines as cross-linkers (diaminobutane and cystamine). Disulfide bridges were cleaved to thiol groups and the polymer backbone was further modified with RGD sequence. Biodegradability of the hydrogels was evaluated by experiments on the base of enzymes and cell culture medium. Poly(aspartic acid) hydrogels possessing only disulfide bridges as cross-links proved to be degradable by collagenase I. The MG-63 cells showed healthy, fibroblast-like morphology on the double cross-linked and RGD modified hydrogels. Thiolated poly(aspartic acid) based hydrogels provide ideal conditions for adhesion, survival, proliferation, and migration of osteoblast-like cells. The highest viability was found on the thiolated PASP gels while the RGD motif had influence on compacted cluster formation of the cells. These biodegradable and biocompatible poly(aspartic acid)-based hydrogels are promising scaffolds for cell cultivation.

Mathematical modeling of acid-base physiology

PubMed Central

Occhipinti, Rossana; Boron, Walter F.

2015-01-01

pH is one of the most important parameters in life, influencing virtually every biological process at the cellular, tissue, and whole-body level. Thus, for cells, it is critical to regulate intracellular pH (pHi) and, for multicellular organisms, to regulate extracellular pH (pHo). pHi regulation depends on the opposing actions of plasma-membrane transporters that tend to increase pHi, and others that tend to decrease pHi. In addition, passive fluxes of uncharged species (e.g., CO2, NH3) and charged species (e.g., HCO3− , NH4+) perturb pHi. These movements not only influence one another, but also perturb the equilibria of a multitude of intracellular and extracellular buffers. Thus, even at the level of a single cell, perturbations in acid-base reactions, diffusion, and transport are so complex that it is impossible to understand them without a quantitative model. Here we summarize some mathematical models developed to shed light onto the complex interconnected events triggered by acids-base movements. We then describe a mathematical model of a spherical cell–which to our knowledge is the first one capable of handling a multitude of buffer reaction–that our team has recently developed to simulate changes in pHi and pHo caused by movements of acid-base equivalents across the plasma membrane of a Xenopus oocyte. Finally, we extend our work to a consideration of the effects of simultaneous CO2 and HCO3− influx into a cell, and envision how future models might extend to other cell types (e.g., erythrocytes) or tissues (e.g., renal proximal-tubule epithelium) important for whole-body pH homeostasis. PMID:25617697

[Development and practice evaluation of blood acid-base imbalance analysis software].

PubMed

Chen, Bo; Huang, Haiying; Zhou, Qiang; Peng, Shan; Jia, Hongyu; Ji, Tianxing

2014-11-01

To develop a blood gas, acid-base imbalance analysis computer software to diagnose systematically, rapidly, accurately and automatically determine acid-base imbalance type, and evaluate the clinical application. Using VBA programming language, a computer aided diagnostic software for the judgment of acid-base balance was developed. The clinical data of 220 patients admitted to the Second Affiliated Hospital of Guangzhou Medical University were retrospectively analyzed. The arterial blood gas [pH value, HCO(3)(-), arterial partial pressure of carbon dioxide (PaCO₂)] and electrolytes included data (Na⁺ and Cl⁻) were collected. Data were entered into the software for acid-base imbalances judgment. At the same time the data generation was calculated manually by H-H compensation formula for determining the type of acid-base imbalance. The consistency of judgment results from software and manual calculation was evaluated, and the judgment time of two methods was compared. The clinical diagnosis of the types of acid-base imbalance for the 220 patients: 65 cases were normal, 90 cases with simple type, mixed type in 41 cases, and triplex type in 24 cases. The accuracy of the judgment results of the normal and triplex types from computer software compared with which were calculated manually was 100%, the accuracy of the simple type judgment was 98.9% and 78.0% for the mixed type, and the total accuracy was 95.5%. The Kappa value of judgment result from software and manual judgment was 0.935, P=0.000. It was demonstrated that the consistency was very good. The time for software to determine acid-base imbalances was significantly shorter than the manual judgment (seconds:18.14 ± 3.80 vs. 43.79 ± 23.86, t=7.466, P=0.000), so the method of software was much faster than the manual method. Software judgment can replace manual judgment with the characteristics of rapid, accurate and convenient, can improve work efficiency and quality of clinical doctors and has great

Effects of Sodium Benzoate Treatment in Combination with An Extinction Training on the Maintenance of Cocaine-Supported Memory.

PubMed

Tsai, Yi-Ni; Tzeng, Wen-Yu; Cherng, Chianfang G; Liao, Tien You; Wu, Hsin-Hua; Lin, Jie-Kuan; Yu, Lung

2016-02-29

Activation of N-methyl-D-aspartate (NMDA) receptor can facilitate the extinction of various maladaptive memories. Sodium benzoate (NaB) has been known to enhance a naturally occurring full agonist on the glycine binding site of the NMDA receptor. This study aimed to test whether systemic NaB treatment can affect the extinction of a cocaine-supported memory, the cocaine-induced conditioned place preference (CPP). Following the establishment of the cocaine (10 mg/kg/conditioning × 3)-induced CPP, an extinction protocol, consisting of two consecutive extinction training bouts at an 8-h interval, was used. NaB (500 mg/kg) or an equivalent volume of saline was given immediately following each extinction training bout to test the modulating effect of NaB on the maintenance of cocaine-induced CPP. Moreover, NaB was bilaterally micro-infused into the medial prefrontal cortex (mPFC) to validate the involvement of this brain region in mediating systemic NaB treatment-produced effect on cocaine-induced CPP. Systemic (500 mg/kg) and intra-mPFC (10 μg/side) NaB treatment significantly decreased subsequent cocaine-induced CPP magnitude, although the NaB treatment or the extinction training alone did not affect such CPP magnitude. It was of importance to note that systemic or intra-mPFC NaB delivery did not affect mouse locomotor activity in the retests. These results, taken together, suggest that NaB treatment in combination with the extinction training may facilitate the extinction of the cocaine-supported memory. Moreover, systemic NaB treatment exerts such effects, at least in part, via its effect in the mPFC.

Study of the acid-base properties of mineral soil horizons using pK spectroscopy

NASA Astrophysics Data System (ADS)

Shamrikova, E. V.; Vanchikova, E. V.; Ryazanov, M. A.

2007-11-01

The presence of groups 4 and 5 participating in acid-base equilibria was revealed in samples from mineral horizons of the gley-podzolic soil of the Komi Republic using pK spectroscopy (the mathematical processing of potentiometric titration curves for plotting the distribution of acid groups according to their pK values). The specific quantity of acid-base sites in soil samples was calculated. The contribution of organic and mineral soil components to the groups of acid-base sites was estimated. The pK values of groups determining the potential, exchangeable, and unexchangeable acidities were found. The heterogeneity of acid components determining different types of soil acidity was revealed.

Adsorption of nucleic acid bases and amino acids on single-walled carbon and boron nitride nanotubes: a first-principles study.

PubMed

Zheng, Jiaxin; Song, Wei; Wang, Lu; Lu, Jing; Luo, Guangfu; Zhou, Jing; Qin, Rui; Li, Hong; Gao, Zhengxiang; Lai, Lin; Li, Guangping; Mei, Wai Ning

2009-11-01

We study the adsorptions of nucleic acid bases adenine (A), cytosine (C), guanine (G), thymine (T), and uracil (U) and four amino acids phenylalanine, tyrosine, tryptophan, alanine on the single-walled carbon nanotubes (SWCNTs) and boron nitride nanotubes (SWBNNTs) by using density functional theory. We find that the aromatic content plays a critical role in the adsorption. The adsorptions of nucleic acid bases and amino acids on the (7, 7) SWBNNT are stronger than those on the (7, 7) SWCNT. Oxidative treatment of SWCNTs favors the adsorption of biomolecules on nanotubes.

Elongated and substituted triazine-based tricarboxylic acid linkers for MOFs.

PubMed

Klinkebiel, Arne; Beyer, Ole; Malawko, Barbara; Lüning, Ulrich

2016-01-01

New triazine-based tricarboxylic acid linkers were prepared as elongated relatives of triazinetribenzoic acid (TATB). Additionally, functional groups (NO 2 , NH 2 , OMe, OH) were introduced for potential post-synthetic modification (PSM) of MOFs. Functionalized tris(4-bromoaryl)triazine "cores" ( 3a , 3b ) were obtained by unsymmetric trimerization mixing one equivalent of an acid chloride (OMe or NO 2 substituted) with two equivalents of an unsubstituted nitrile. Triple Suzuki coupling of the cores 3 with suitable phenyl- and biphenylboronic acid derivatives provided elongated tricarboxylic acid linkers as carboxylic acids 17 and 20 or their esters 16 and 19 . Reduction of the nitro group and cleavage of the methoxy group gave the respective amino and hydroxy-substituted triazine linkers.

A mathematical model of pH, based on the total stoichiometric concentration of acids, bases and ampholytes dissolved in water.

PubMed

Mioni, Roberto; Mioni, Giuseppe

2015-10-01

In chemistry and in acid-base physiology, the Henderson-Hasselbalch equation plays a pivotal role in studying the behaviour of the buffer solutions. However, it seems that the general function to calculate the valence of acids, bases and ampholytes, N = f(pH), at any pH, has only been provided by Kildeberg. This equation can be applied to strong acids and bases, pluriprotic weak acids, bases and ampholytes, with an arbitrary number of acid strength constants, pKA, including water. By differentiating this function with respect to pH, we obtain the general equation for the buffer value. In addition, by integrating the titration curve, TA, proposed by Kildeberg, and calculating its Legendre transform, we obtain the Gibbs free energy of pH (or pOH)-dependent titratable acid. Starting from the law of electroneutrality and applying suitable simplifications, it is possible to calculate the pH of the buffer solutions by numerical methods, available in software packages such as Excel. The concept of buffer capacity has also been clarified by Urbansky, but, at variance with our approach, not in an organic manner. In fact, for each set of monobasic, dibasic, tribasic acids, etc., various equations are presented which independently fit each individual acid-base category. Consequently, with the increase in acid groups (pKA), the equations become more and more difficult, both in practice and in theory. Some examples are proposed to highlight the boundary that exists between acid-base physiology and the thermodynamic concepts of energy, chemical potential, amount of substance and acid resistance.

A Novel Plasmid-Based Microarray Screen Identifies Suppressors of rrp6Δ in Saccharomyces cerevisiae▿†

PubMed Central

Abruzzi, Katharine; Denome, Sylvia; Olsen, Jens Raabjerg; Assenholt, Jannie; Haaning, Line Lindegaard; Jensen, Torben Heick; Rosbash, Michael

2007-01-01

Genetic screens in Saccharomyces cerevisiae provide novel information about interacting genes and pathways. We screened for high-copy-number suppressors of a strain with the gene encoding the nuclear exosome component Rrp6p deleted, with either a traditional plate screen for suppressors of rrp6Δ temperature sensitivity or a novel microarray enhancer/suppressor screening (MES) strategy. MES combines DNA microarray technology with high-copy-number plasmid expression in liquid media. The plate screen and MES identified overlapping, but also different, suppressor genes. Only MES identified the novel mRNP protein Nab6p and the tRNA transporter Los1p, which could not have been identified in a traditional plate screen; both genes are toxic when overexpressed in rrp6Δ strains at 37°C. Nab6p binds poly(A)+ RNA, and the functions of Nab6p and Los1p suggest that mRNA metabolism and/or protein synthesis are growth rate limiting in rrp6Δ strains. Microarray analyses of gene expression in rrp6Δ strains and a number of suppressor strains support this hypothesis. PMID:17101774

Multiple human papillomavirus infections and type-competition in women from a clinic attendee population in China.

PubMed

Nie, Jianhui; Liu, Jianhua; Xie, Hui; Sun, Zhengrong; Zhao, Juan; Chen, Qingqing; Liu, Yangyang; Huang, Weijin; Ruan, Qiang; Wang, Youchun

2016-11-01

To investigate the multi-infection patterns and type competition for human papillomavirus (HPV) in Chinese clinic attending women and evaluate the association between the infection status and cancer risk. Three hundred and thirty-two HPV-DNA-positive samples were genotyped for 21 HPVs and tested for 13 types of HPV neutralizing antibody using pseudoviron-based assay. Odds ratios (ORs) were calculated to evaluate the coinfection patterns for both DNA and neutralizing antibody (NAb), and the associations of HSIL+ with HPV DNA and NAb. Of the 332 HPV-DNA-positive subjects, 279 (84.0%) were detected as NAb positive. Multi-positive results were identified in 23.2% (77/332) HPV DNA tests and 60.2% (168/279) HPV NAb assays. The NAb titers for the multiple-positive samples (geometric mean 214) were significantly higher than the single-positive samples (geometric mean 114) (P < 0.01). HPV16-HPV52 was identified as a type-competition pair for both HPV DNA (OR = 0.09; 95%CI = 0.02-0.42) and NAb (OR = 0.27; 95%CI = 0.11-0.69) data. Compared to other types, HPV16 DNA was associated significantly with high risk of HSIL+ (OR = 2.57; 95%CI = 1.23-5.38). HPV16-HPV52 was identified as a potential type-competition pair, which might result in the type modulation with the implementation of the approved bi- or quadri-valent vaccines. J. Med. Virol. 88:1989-1998, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

High School Students' Concepts of Acids and Bases.

ERIC Educational Resources Information Center

Ross, Bertram H. B.

An investigation of Ontario high school students' understanding of acids and bases with quantitative and qualitative methods revealed misconceptions. A concept map, based on the objectives of the Chemistry Curriculum Guideline, generated multiple-choice items and interview questions. The multiple-choice test was administered to 34 grade 12…

Collaborative Strategies for Teaching Common Acid-Base Disorders to Medical Students

ERIC Educational Resources Information Center

Petersen, Marie Warrer; Toksvang, Linea Natalie; Plovsing, Ronni R.; Berg, Ronan M. G.

2014-01-01

The ability to recognize and diagnose acid-base disorders is of the utmost importance in the clinical setting. However, it has been the experience of the authors that medical students often have difficulties learning the basic principles of acid-base physiology in the respiratory physiology curriculum, particularly when applying this knowledge to…

Students' Understanding of Acid, Base and Salt Reactions in Qualitative Analysis.

ERIC Educational Resources Information Center

Tan, Kim-Chwee Daniel; Goh, Ngoh-Khang; Chia, Lian-Sai; Treagust, David F.

2003-01-01

Uses a two-tier, multiple-choice diagnostic instrument to determine (n=915) grade 10 students' understanding of the acid, base, and salt reactions involved in basic qualitative analysis. Reports that many students did not understand the formation of precipitates and the complex salts, acid/salt-base reactions, and thermal decomposition involved in…

Acid-base alterations in heatstroke.

PubMed

Bouchama, A; De Vol, E B

2001-04-01

To analyze the acid-base balance during heatstroke. Retrospective study. Heatstroke Center, Makkah, Saudi Arabia. Hundred nine consecutive heatstroke patients (mean age 55 +/- 12 years) with rectal temperature from 40 to 43.4 degrees C following exposure to hot weather. Arterial blood gases collected prospectively and analyzed using 95% confidence limits established by controlled experimental studies. Severity of heatstroke on admission assessed by Simplified Acute Physiology Score and Organ System Failure score. Metabolic acidosis was the predominant acid-base change followed by respiratory alkalosis (81 and 55% of the patients, respectively). The prevalence of metabolic acidosis (but not respiratory alkalosis) was significantly associated with the degree of hyperthermia: 63, 95 and 100% at 41, 42 and 43 degrees C, respectively (p < 0.0001). Patients with metabolic acidosis had a large anion gap (24 +/- 5). Arterial partial pressure of oxygen (PaO2), systolic blood pressure and Organ System Failure score were similar with or without metabolic acidosis. Although the acute physiology score was higher in patients with, than without, metabolic acidosis (15.7 +/- 3.7 vs 9.8 +/- 4.4, p < 0.001), there was no significant difference in neurologic morbidity and mortality (7.9 vs 1.1%, 5.6 vs 0%, p = 0.776 and 0.581, respectively). We conclude that metabolic acidosis is the predominant response in heatstroke.

Efficient aspartic acid production by a psychrophile-based simple biocatalyst.

PubMed

Tajima, Takahisa; Hamada, Mai; Nakashimada, Yutaka; Kato, Junichi

2015-10-01

We previously constructed a Psychrophile-based Simple bioCatalyst (PSCat) reaction system, in which psychrophilic metabolic enzymes are inactivated by heat treatment, and used it here to study the conversion of aspartic acid from fumaric acid mediated by the activity of aspartate ammonia-lyase (aspartase). In Escherichia coli, the biosynthesis of aspartic acid competes with that of L-malic acid produced from fumaric acid by fumarase. In this study, E. coli aspartase was expressed in psychrophilic Shewanella livingstonensis Ac10 heat treated at 50 °C for 15 min. The resultant PSCat could convert fumaric acid to aspartic acid without the formation of L-malic acid because of heat inactivation of psychrophilic fumarase activity. Furthermore, alginate-immobilized PSCat produced high yields of aspartic acid and could be re-used nine times. The results of our study suggest that PSCat can be applied in biotechnological production as a new approach to increase the yield of target compounds.

Acid-base properties of Baltic Sea dissolved organic matter

NASA Astrophysics Data System (ADS)

Hammer, Karoline; Schneider, Bernd; Kuliński, Karol; Schulz-Bull, Detlef E.

2017-09-01

Calculations related to the marine CO2 system that are based on alkalinity data may be strongly biased if the contributions of organic compounds are ignored. In coastal seas, concentrations of dissolved organic matter (DOM) are frequently high and alkalinity from inorganic compounds is low. In this study, based on measurements of total alkalinity, total CO2, and pH, we determined the organic alkalinity, Aorg, in water from the central Baltic Sea. The maximum Aorg measured in the surface mixed layer during the spring bloom was > 50 μmol/kg-SW but the Aorg decreased with depth and approached zero below the permanent halocline. This behavior could be attributed to the decreased pH of deeper water layers. The data were used to calculate the bulk dissociation constant, KDOM, for marine DOM and the fraction f of dissolved organic carbon (DOC) that acts as a carrier for acid-base functional groups. The p KDOM (7.27) agreed well with the value (7.34) previously estimated in a preliminary study of organic alkalinity in the Baltic Sea. The fraction of carbon atoms carrying acid-base groups was 17% and was somewhat higher than previously reported (12%). Spike experiments performed using artificial seawater and three different humic/fulvic substances tested whether the acid-base properties of these substances explain the results of our field study. Specifically, Aorg was determined at different concentrations (DOC) of the added humic/fulvic substances. The relationship between Aorg and the DOC concentrations indicated that humic/fulvic substances are more acidic (p KDOM < 6.5) than the bulk DOC natural occurring in the Baltic Sea.

A Special Connection between γδ T Cells and Natural Antibodies?

PubMed Central

Born, Willi K.; Huang, Yafei; Zeng, Wanjiang; Torres, Raul M.; O’Brien, Rebecca L.

2017-01-01

Natural antibodies (NAbs) play an important role in early host defense, autophagy and tissue remodeling, and in immune regulation. They arise spontaneously (without specific immunization), and are already present at birth. NAbs are produced by B1 B cells, MZ B cells and other B cell types. They include all major Ig subclasses but IgM antibodies are prevalent, especially early in development. NAbs may be poly-specific, recognize particular auto-antigens, or detect neo-determinants such as those exposed during apoptosis or generated by oxidation. NAbs do not require cognate T cell help but depend on soluble mediators produced by T cells. Our recent studies suggest that γδ T cells may have a special relationship with NAbs, and play a prominent role in their regulation, in part through the fine-tuning of IL-4-levels. The spontaneously activated state of these cells likely enables their cytokine production and other functions in the absence of external stimulation. Ontogenetically, the earlier arising γδ T cells are better positioned than αβ T cells to shape the developing repertoire of NAbs. Intriguingly, ligand specificities of NAbs and γδ T cell receptors appear to be overlapping, perhaps allowing γδ cognate help for certain NAb specificities. Via NAbs, γδ T cells could exert a regulatory influence on numerous processes in health and disease. PMID:27235134

A Special Connection between γδ T Cells and Natural Antibodies?

PubMed

Born, Willi K; Huang, Yafei; Zeng, Wanjiang; Torres, Raul M; O'Brien, Rebecca L

2016-12-01

Natural antibodies (NAbs) play an important role in early host defense, autophagy and tissue remodeling, and in immune regulation. They arise spontaneously (without specific immunization), and are already present at birth. NAbs are produced by B1 B cells, MZ B cells and other B cell types. They include all major Ig subclasses but IgM antibodies are prevalent, especially early in development. NAbs may be poly-specific, recognize particular auto-antigens, or detect neo-determinants such as those exposed during apoptosis or generated by oxidation. NAbs do not require cognate T cell help but depend on soluble mediators produced by T cells. Our recent studies suggest that γδ T cells may have a special relationship with NAbs, and play a prominent role in their regulation, in part through the fine-tuning of IL-4 levels. The spontaneously activated state of these cells likely enables their cytokine production and other functions in the absence of external stimulation. Ontogenetically, the earlier arising γδ T cells are better positioned than αβ T cells to shape the developing repertoire of NAbs. Intriguingly, ligand specificities of NAbs and γδ T cell receptors appear to be overlapping, perhaps allowing γδ cognate help for certain NAb specificities. Via NAbs, γδ T cells could exert a regulatory influence on numerous processes in health and disease.

Ecological validity of the screening module and the Daily Living tests of the Neuropsychological Assessment Battery using the Mayo-Portland Adaptability Inventory-4 in postacute brain injury rehabilitation.

PubMed

Zgaljardic, Dennis J; Yancy, Sybil; Temple, Richard O; Watford, Monica F; Miller, Rebekah

2011-11-01

The assessment of ecological validity of neuropsychological measures is an area of growing interest, particularly in the postacute brain injury rehabilitation (PABIR) setting, as there is an increasing demand for clinicians to address functional and real-world outcomes. In the current study, we assessed the predictive value of the Screening module and the Daily Living tests of the Neuropsychological Assessment Battery (NAB) using clinician ratings from the Mayo-Portland Adaptability Inventory-4 (MPAI-4) in patients with moderate to severe traumatic brain injury. Forty-seven individuals were each administered the NAB Screening module (NAB-SM) and the NAB Daily Living (NAB-DL) tests following admission to a residential PABIR program. MPAI-4 ratings were also obtained at admission. Linear regression analysis was used to examine the association between these functional and neuropsychological assessment measures. We replicated prior work (Temple at al., 2009) and expanded evidence for the ecological validity of the NAB-SM. Furthermore, our findings support the ecological validity of the NAB-DL Bill Payment, Judgment, and Map Reading tests with regards to functional skills and real-world activities. The current study supports prior work from our lab assessing the predictive value of the NAB-SM, as well as provides evidence for the ecological validity for select NAB-DL tests in patients with moderate to severe traumatic brain injury admitted to a residential PABIR program.

Selective Chemical Conversion of Sugars in Aqueous Solutions without Alkali to Lactic Acid Over a Zn-Sn-Beta Lewis Acid-Base Catalyst

NASA Astrophysics Data System (ADS)

Dong, Wenjie; Shen, Zheng; Peng, Boyu; Gu, Minyan; Zhou, Xuefei; Xiang, Bo; Zhang, Yalei

2016-05-01

Lactic acid is an important platform molecule in the synthesis of a wide range of chemicals. However, in aqueous solutions without alkali, its efficient preparation via the direct catalysis of sugars is hindered by a side dehydration reaction to 5-hydroxymethylfurfural due to Brønsted acid, which originates from organic acids. Herein, we report that a previously unappreciated combination of common two metal mixed catalyst (Zn-Sn-Beta) prepared via solid-state ion exchange synergistically promoted this reaction. In water without a base, a conversion exceeding 99% for sucrose with a lactic acid yield of 54% was achieved within 2 hours at 190 °C under ambient air pressure. Studies of the acid and base properties of the Zn-Sn-Beta zeolite suggest that the introduction of Zn into the Sn-Beta zeolite sequentially enhanced both the Lewis acid and base sites, and the base sites inhibited a series of side reactions related to fructose dehydration to 5-hydroxymethylfurfural and its subsequent decomposition.

Intracellular pH regulation by acid-base transporters in mammalian neurons

PubMed Central

Ruffin, Vernon A.; Salameh, Ahlam I.; Boron, Walter F.; Parker, Mark D.

2014-01-01

Intracellular pH (pHi) regulation in the brain is important in both physiological and physiopathological conditions because changes in pHi generally result in altered neuronal excitability. In this review, we will cover 4 major areas: (1) The effect of pHi on cellular processes in the brain, including channel activity and neuronal excitability. (2) pHi homeostasis and how it is determined by the balance between rates of acid loading (JL) and extrusion (JE). The balance between JE and JL determine steady-state pHi, as well as the ability of the cell to defend pHi in the face of extracellular acid-base disturbances (e.g., metabolic acidosis). (3) The properties and importance of members of the SLC4 and SLC9 families of acid-base transporters expressed in the brain that contribute to JL (namely the Cl-HCO3 exchanger AE3) and JE (the Na-H exchangers NHE1, NHE3, and NHE5 as well as the Na+- coupled HCO3− transporters NBCe1, NBCn1, NDCBE, and NBCn2). (4) The effect of acid-base disturbances on neuronal function and the roles of acid-base transporters in defending neuronal pHi under physiopathologic conditions. PMID:24592239

The in Silico Insight into Carbon Nanotube and Nucleic Acid Bases Interaction.

PubMed

Karimi, Ali Asghar; Ghalandari, Behafarid; Tabatabaie, Seyed Saleh; Farhadi, Mohammad

2016-05-01

To explore practical applications of carbon nanotubes (CNTs) in biomedical fields the properties of their interaction with biomolecules must be revealed. Recent years, the interaction of CNTs with biomolecules is a subject of research interest for practical applications so that previous research explored that CNTs have complementary structure properties with single strand DNA (ssDNA). Hence, the quantum mechanics (QM) method based on ab initio was used for this purpose. Therefore values of binding energy, charge distribution, electronic energy and other physical properties of interaction were studied for interaction of nucleic acid bases and SCNT. In this study, the interaction between nucleic acid bases and a (4, 4) single-walled carbon nanotube (SCNT) were investigated through calculations within quantum mechanics (QM) method at theoretical level of Hartree-Fock (HF) method using 6-31G basis set. Hence, the physical properties such as electronic energy, total dipole moment, charge distributions and binding energy of nucleic acid bases interaction with SCNT were investigated based on HF method. It has been found that the guanine base adsorption is bound stronger to the outer surface of nanotube in comparison to the other bases, consistent with the recent theoretical studies. In the other words, the results explored that guanine interaction with SCNT has optimum level of electronic energy so that their interaction is stable. Also, the calculations illustrated that SCNT interact to nucleic acid bases by noncovalent interaction because of charge distribution an electrostatic area is created in place of interaction. Consequently, small diameter SCNT interaction with nucleic acid bases is noncovalent. Also, the results revealed that small diameter SCNT interaction especially SCNT (4, 4) with nucleic acid bases can be useful in practical application area of biomedical fields such detection and drug delivery.

Relativistic effects on acidities and basicities of Brønsted acids and bases containing gold.

PubMed

Koppel, Ilmar A; Burk, Peeter; Kasemets, Kalev; Koppel, Ivar

2013-11-07

It is usually believed that relativistic effects as described by the Dirac-Schrödinger equation (relative to the classical or time-independent Schrödinger equation) are of little importance in chemistry. A closer look, however, reveals that some important and widely known properties (e.g., gold is yellow, mercury is liquid at room temperature) stem from relativistic effects. So far the influence of relativistic effects on the acid-base properties has been mostly ignored. Here we show that at least for compounds of gold such omission is completely erroneous and would lead to too high basicity and too low acidity values with errors in the range of 25-55 kcal mol(-1) (or 20 to 44 powers of ten in pK(a) units) in the gas-phase. These findings have important implications for the design of new superstrong acids and bases, and for the understanding of gold-catalysed reactions.

Aerosol Fragmentation Driven by Coupling of Acid-Base and Free-Radical Chemistry in the Heterogeneous Oxidation of Aqueous Citric Acid by OH Radicals.

PubMed

Liu, Matthew J; Wiegel, Aaron A; Wilson, Kevin R; Houle, Frances A

2017-08-10

A key uncertainty in the heterogeneous oxidation of carboxylic acids by hydroxyl radicals (OH) in aqueous-phase aerosol is how the free-radical reaction pathways might be altered by acid-base chemistry. In particular, if acid-base reactions occur concurrently with acyloxy radical formation and unimolecular decomposition of alkoxy radicals, there is a possibility that differences in reaction pathways impact the partitioning of organic carbon between the gas and aqueous phases. To examine these questions, a kinetic model is developed for the OH-initiated oxidation of citric acid aerosol at high relative humidity. The reaction scheme, containing both free-radical and acid-base elementary reaction steps with physically validated rate coefficients, accurately predicts the experimentally observed molecular composition, particle size, and average elemental composition of the aerosol upon oxidation. The difference between the two reaction channels centers on the reactivity of carboxylic acid groups. Free-radical reactions mainly add functional groups to the carbon skeleton of neutral citric acid, because carboxylic acid moieties deactivate the unimolecular fragmentation of alkoxy radicals. In contrast, the conjugate carboxylate groups originating from acid-base equilibria activate both acyloxy radical formation and carbon-carbon bond scission of alkoxy radicals, leading to the formation of low molecular weight, highly oxidized products such as oxalic and mesoxalic acid. Subsequent hydration of carbonyl groups in the oxidized products increases the aerosol hygroscopicity and accelerates the substantial water uptake and volume growth that accompany oxidation. These results frame the oxidative lifecycle of atmospheric aerosol: it is governed by feedbacks between reactions that first increase the particle oxidation state, then eventually promote water uptake and acid-base chemistry. When coupled to free-radical reactions, acid-base channels lead to formation of low molecular

Electrolyte and acid-base abnormalities associated with purging behaviors.

PubMed

Mehler, Philip S; Walsh, Kristine

2016-03-01

Eating disorders that are associated with purging behaviors are complicated by frequent blood electrolyte and acid-base abnormalities. Herein, we review the major electrolyte and acid-base abnormalities and their treatment methods. The body of rigorous, eating disorder-specific literature on this topical area is not robust enough to perform a systematic review as defined by PRISMA guidelines. Therefore, a qualitative review of mostly medical literature was conducted. Hypokalemia, hyponatremia, and sodium chloride-responsive metabolic alkalosis are the most common serum changes that occur as a result of purging behaviors. They vary depending on the mode and frequency of purging behaviors. They can all potentially cause dangerous medical complications and are in need of definitive medical treatment. Eating disorders that are associated with purging behaviors are associated with a number of electrolyte and acid-base changes which are complex in their origin, documented to be medically dangerous and this definitive treatment is necessary to help achieve a successful treatment outcome, and in need of definitive treatment as described herein. © 2016 Wiley Periodicals, Inc.

Elongated and substituted triazine-based tricarboxylic acid linkers for MOFs

PubMed Central

Klinkebiel, Arne; Beyer, Ole; Malawko, Barbara

2016-01-01

New triazine-based tricarboxylic acid linkers were prepared as elongated relatives of triazinetribenzoic acid (TATB). Additionally, functional groups (NO2, NH2, OMe, OH) were introduced for potential post-synthetic modification (PSM) of MOFs. Functionalized tris(4-bromoaryl)triazine “cores” (3a,3b) were obtained by unsymmetric trimerization mixing one equivalent of an acid chloride (OMe or NO2 substituted) with two equivalents of an unsubstituted nitrile. Triple Suzuki coupling of the cores 3 with suitable phenyl- and biphenylboronic acid derivatives provided elongated tricarboxylic acid linkers as carboxylic acids 17 and 20 or their esters 16 and 19. Reduction of the nitro group and cleavage of the methoxy group gave the respective amino and hydroxy-substituted triazine linkers. PMID:28144293

Structural flexibility of a conserved antigenic region in hepatitis C virus glycoprotein E2 recognized by broadly neutralizing antibodies.

PubMed

Meola, Annalisa; Tarr, Alexander W; England, Patrick; Meredith, Luke W; McClure, C Patrick; Foung, Steven K H; McKeating, Jane A; Ball, Jonathan K; Rey, Felix A; Krey, Thomas

2015-02-01

Neutralizing antibodies (NAbs) targeting glycoprotein E2 are important for the control of hepatitis C virus (HCV) infection. One conserved antigenic site (amino acids 412 to 423) is disordered in the reported E2 structure, but a synthetic peptide mimicking this site forms a β-hairpin in complex with three independent NAbs. Our structure of the same peptide in complex with NAb 3/11 demonstrates a strikingly different extended conformation. We also show that residues 412 to 423 are essential for virus entry but not for E2 folding. Together with the neutralizing capacity of the 3/11 Fab fragment, this indicates an unexpected structural flexibility within this epitope. NAbs 3/11 and AP33 (recognizing the extended and β-hairpin conformations, respectively) display similar neutralizing activities despite converse binding kinetics. Our results suggest that HCV utilizes conformational flexibility as an immune evasion strategy, contributing to the limited immunogenicity of this epitope in patients, similar to the conformational flexibility described for other enveloped and nonenveloped viruses. Approximately 180 million people worldwide are infected with hepatitis C virus (HCV), and neutralizing antibodies play an important role in controlling the replication of this major human pathogen. We show here that one of the most conserved antigenic sites within the major glycoprotein E2 (amino acids 412 to 423), which is disordered in the recently reported crystal structure of an E2 core fragment, can adopt different conformations in the context of the infectious virus particle. Recombinant Fab fragments recognizing different conformations of this antigenic site have similar neutralization activities in spite of converse kinetic binding parameters. Of note, an antibody response targeting this antigenic region is less frequent than those targeting other more immunogenic regions in E2. Our results suggest that the observed conformational flexibility in this conserved antigenic

Fast high-throughput method for the determination of acidity constants by capillary electrophoresis: I. Monoprotic weak acids and bases.

PubMed

Fuguet, Elisabet; Ràfols, Clara; Bosch, Elisabeth; Rosés, Martí

2009-04-24

A new and fast method to determine acidity constants of monoprotic weak acids and bases by capillary zone electrophoresis based on the use of an internal standard (compound of similar nature and acidity constant as the analyte) has been developed. This method requires only two electrophoretic runs for the determination of an acidity constant: a first one at a pH where both analyte and internal standard are totally ionized, and a second one at another pH where both are partially ionized. Furthermore, the method is not pH dependent, so an accurate measure of the pH of the buffer solutions is not needed. The acidity constants of several phenols and amines have been measured using internal standards of known pK(a), obtaining a mean deviation of 0.05 pH units compared to the literature values.

HEPATIC FATTY ACID PROFILE OF RATS FED A TRIHEPTANOIN-BASED KETOGENIC DIET.

PubMed

Vieira de Melo, Ingrid Sofia; Da Rocha Ataide, Terezinha; Lima de Oliveira, Suzana; Bezerra Bueno, Nassib; Duarte de Freitas, Johnnatan; Goulart Sant'Ana, Antônio Euzébio

2015-07-01

the aim of this study was to evaluate the influence of consumption of a ketogenic diet supplemented with triheptanoin, a medium-chain anaplerotic triacylglycerol, on the liver fatty acid profile of Wistar rats. three groups of male Wistar rats (n = 10) were submitted to an AIN-93 control diet, a triheptanoin- based ketogenic diet, or a soybean oil-based ketogenic diet for 60 days. Excised livers were subjected to lipid extraction and methylation to obtain fatty acids methyl esters, which were subjected to gas chromatography- mass spectrometry. compared to the rats fed the control diet, those fed ketogenic diets showed a significant reduction in the concentrations of 9-hexadecenoic and 9-octadecenoic acids, whereas those fed triheptanoin showed increased levels of octadecanoic acid. changes in the liver fatty acid profiles of the rats fed a triheptanoin-based or a soybean oil-based ketogenic diet did not seem to be related to the dietary fat source, but rather to the characteristics of the ketogenic diets themselves. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Evolution of the human immunodeficiency virus type 2 envelope in the first years of infection is associated with the dynamics of the neutralizing antibody response

DOE PAGES

Rocha, Cheila; Calado, Rita; Borrego, Pedro; ...

2013-10-24

Background: therapy and the majority of HIV-2 infected individuals survive as elite controllers with normal CD4 + T cell counts and low or undetectable plasma viral load. Neutralizing antibodies (Nabs) are thought to play a central role in HIV-2 evolution and pathogenesis. However, the dynamic of the Nab response and resulting HIV-2 escape during acute infection and their impact in HIV-2 evolution and disease progression remain largely unknown. Our objective was to characterize the Nab response and the molecular and phenotypic evolution of HIV-2 in association with Nab escape in the first years of infection in two children infected atmore » birth. As a result, CD4 + T cells decreased from about 50% to below 30% in both children in the first five years of infection and the infecting R5 viruses were replaced by X4 viruses within the same period. With antiretroviral therapy, viral load in child 1 decreased to undetectable levels and CD4 + T cells recovered to normal levels, which have been sustained at least until the age of 12. In contrast, viral load increased in child 2 and she progressed to AIDS and death at age 9. Beginning in the first year of life, child 1 raised high titers of antibodies that neutralized primary R5 isolates more effectively than X4 isolates, both autologous and heterologous. Child 2 raised a weak X4-specific Nab response that decreased sharply as disease progressed. Rate of evolution, nucleotide and amino acid diversity, and positive selection, were significantly higher in the envelope of child 1 compared to child 2. Rates of R5-to-X4 tropism switch, of V1 and V3 sequence diversification, and of convergence of V3 to a β-hairpin structure were related with rate of escape from the neutralizing antibodies. Finally, our data suggests that the molecular and phenotypic evolution of the human immunodeficiency virus type 2 envelope are related with the dynamics of the neutralizing antibody response providing further support for a model in which

Evolution of the human immunodeficiency virus type 2 envelope in the first years of infection is associated with the dynamics of the neutralizing antibody response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rocha, Cheila; Calado, Rita; Borrego, Pedro

Background: therapy and the majority of HIV-2 infected individuals survive as elite controllers with normal CD4 + T cell counts and low or undetectable plasma viral load. Neutralizing antibodies (Nabs) are thought to play a central role in HIV-2 evolution and pathogenesis. However, the dynamic of the Nab response and resulting HIV-2 escape during acute infection and their impact in HIV-2 evolution and disease progression remain largely unknown. Our objective was to characterize the Nab response and the molecular and phenotypic evolution of HIV-2 in association with Nab escape in the first years of infection in two children infected atmore » birth. As a result, CD4 + T cells decreased from about 50% to below 30% in both children in the first five years of infection and the infecting R5 viruses were replaced by X4 viruses within the same period. With antiretroviral therapy, viral load in child 1 decreased to undetectable levels and CD4 + T cells recovered to normal levels, which have been sustained at least until the age of 12. In contrast, viral load increased in child 2 and she progressed to AIDS and death at age 9. Beginning in the first year of life, child 1 raised high titers of antibodies that neutralized primary R5 isolates more effectively than X4 isolates, both autologous and heterologous. Child 2 raised a weak X4-specific Nab response that decreased sharply as disease progressed. Rate of evolution, nucleotide and amino acid diversity, and positive selection, were significantly higher in the envelope of child 1 compared to child 2. Rates of R5-to-X4 tropism switch, of V1 and V3 sequence diversification, and of convergence of V3 to a β-hairpin structure were related with rate of escape from the neutralizing antibodies. Finally, our data suggests that the molecular and phenotypic evolution of the human immunodeficiency virus type 2 envelope are related with the dynamics of the neutralizing antibody response providing further support for a model in which

Thermoset coatings from epoxidized sucrose soyate and blocked, bio-based dicarboxylic acids.

PubMed

Kovash, Curtiss S; Pavlacky, Erin; Selvakumar, Sermadurai; Sibi, Mukund P; Webster, Dean C

2014-08-01

A new 100% bio-based thermosetting coating system was developed from epoxidized sucrose soyate crosslinked with blocked bio-based dicarboxylic acids. A solvent-free, green method was used to block the carboxylic acid groups and render the acids miscible with the epoxy resin. The thermal reversibility of this blocking allowed for the formulation of epoxy-acid thermoset coatings that are 100% bio-based. This was possible due to the volatility of the vinyl ethers under curing conditions. These systems have good adhesion to metal substrates and perform well under chemical and physical stress. Additionally, the hardness of the coating system is dependent on the chain length of the diacid used, making it tunable. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Macro-/Nano- Materials Based Ultrasensitive Lateral Flow Nucleic Acid Biosensors

NASA Astrophysics Data System (ADS)

Takalkar, Sunitha

Ultrasensitive detection of nucleic acids plays a very important role in the field of molecular diagnosis for the detection of various diseases. Lateral flow biosensors (LFB) are convenient, easy-to-use, patient friendly forms of detection methods offering rapid and convenient clinical testing in close proximity to the patients thus drawing a lot of attention in different areas of research over the years. In comparison with the traditional immunoassays, the nucleic acid based lateral flow biosensors (NABLFB) has several advantages in terms of stability and interference capabilities. NABLFB utilizes nucleic acid probes as the bio-recognition element. The target analyte typically is the oligonucleotide like the DNA, mRNA, miRNA which are among the nucleic acid secretions by the tumor cells when it comes to detection of cancer. Traditionally gold nanoparticles (GNPs) have been used as labels for conjugating with the detection probes for the qualitative and semi quantitative analysis, the application of GNP-based LFB is limited by its low sensitivity. This dissertation describes the use of different nanomaterials and advanced detection technologies to enhance the sensitivities of the LFB based methods. Silica Nanorods decorated with GNP were synthesized and employed as labels for ultrasensitive detection of miRNA on the LFB. Owing to the biocompatibility and convenience in surface modification of SiNRs, they acted as good carriers to load numerous GNPs. The sensitivity of the GNP-SiNR-based LFSB was enhanced six times compared to the previous GNP-based LFSB. A fluorescent carbon nanoparticle (FCN) was first used as a tag to develop a lateral flow nucleic acid biosensor for ultrasensitive and quantitative detection of nucleic acid samples. Under optimal conditions, the FCN-based LFNAB was capable of detecting minimum 0.4 fM target DNA without complex operations and additional signal amplification. The carbon nanotube was used as a label and carrier of numerous enzyme

Dynamical Approach to Multiequilibria Problems for Mixtures of Acids and Their Conjugated Bases

ERIC Educational Resources Information Center

Glaser, Rainer E.; Delarosa, Marco A.; Salau, Ahmed Olasunkanmi; Chicone, Carmen

2014-01-01

Mathematical methods are described for the determination of steady-state concentrations of all species in multiequilibria systems consisting of several acids and their conjugated bases in aqueous solutions. The main example consists of a mixture of a diprotic acid H[subscript 2]A, a monoprotic acid HB, and their conjugate bases. The reaction…

Hard and soft acids and bases: structure and process.

PubMed

Reed, James L

2012-07-05

Under investigation is the structure and process that gives rise to hard-soft behavior in simple anionic atomic bases. That for simple atomic bases the chemical hardness is expected to be the only extrinsic component of acid-base strength, has been substantiated in the current study. A thermochemically based operational scale of chemical hardness was used to identify the structure within anionic atomic bases that is responsible for chemical hardness. The base's responding electrons have been identified as the structure, and the relaxation that occurs during charge transfer has been identified as the process giving rise to hard-soft behavior. This is in contrast the commonly accepted explanations that attribute hard-soft behavior to varying degrees of electrostatic and covalent contributions to the acid-base interaction. The ability of the atomic ion's responding electrons to cause hard-soft behavior has been assessed by examining the correlation of the estimated relaxation energies of the responding electrons with the operational chemical hardness. It has been demonstrated that the responding electrons are able to give rise to hard-soft behavior in simple anionic bases.

New Inducible Nitric Oxide Synthase and Cyclooxygenase-2 Inhibitors, Nalidixic Acid Linked to Isatin Schiff Bases via Certain l-Amino Acid Bridges.

PubMed

Naglah, Ahmed M; Ahmed, Atallah F; Wen, Zhi-Hong; Al-Omar, Mohamed A; Amr, Abd El-Galil E; Kalmouch, Atef

2016-04-15

A series of new Schiff bases were synthesized by condensation of isatins with the nalidixic acid-l-amino acid hydrazides. Prior to hydrazide formation, a peptide linkage has been prepared via coupling of nalidixic acid with appropriate l-amino acid methyl esters to yield 3a-c. The chemical structures of the new Schiff bases (5b and 5d-h) were confirmed by means of IR, NMR, mass spectroscopic, and elemental analyses. The anti-inflammatory activity of these Schiff bases was evaluated via measurement of the expressed inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells model. The Schiff bases exhibited significant dual inhibitory effect against the induction of the pro-inflammatory iNOS and COX-2 proteins with variable potencies. However, they strongly down-regulated the iNOS expression to the level of 16.5% ± 7.4%-42.2% ± 19.6% compared to the effect on COX-2 expression (<56.4% ± 3.1% inhibition) at the same concentration (10 μM). The higher iNOS inhibition activity of the tested Schiff bases, relative to that of COX-2, seems to be a reflection of the combined suppressive effects exerted by their nalidixic acid, isatins (4a-c), and l-amino acid moieties against iNOS expression. These synthesized nalidixic acid-l-amino acid-isatin conjugates can be regarded as a novel class of anti-inflammatory antibacterial agents.

Dynamic Buffer Capacity in Acid-Base Systems.

PubMed

Michałowska-Kaczmarczyk, Anna M; Michałowski, Tadeusz

The generalized concept of 'dynamic' buffer capacity β V is related to electrolytic systems of different complexity where acid-base equilibria are involved. The resulting formulas are presented in a uniform and consistent form. The detailed calculations are related to two Britton-Robinson buffers, taken as examples.

Novel and economic acid-base indicator based on (p-toluidine) oligomer: Synthesis; characterization and solvatochromism applications

NASA Astrophysics Data System (ADS)

Zoromba, M. Sh.

2017-12-01

A new (p-toluidine) oligomer (PTO) was facile synthesized and economically routed via chemical oxidative polymerization by potassium dichromate as an initiator in an acidic aqueous medium at room temperature. The characterization of (p-toluidine) oligomer (PTO) has been described by various techniques including Fourier transform infra-red (FTIR), UV-Visible measurements, Mass spectra, H NMR, and thermal gravimetric analysis (TGA). Solvatochromism of PTO was studied in different polaritiy solvents such as acetic acid, acetone, dimethyl formamide, ethanol, isopropanol, chloroform, p-xylene, dichloromethane and carbon teterachloride. The absorption bands were bathochromically shifted with increased polarity of the solvent (positive solvatochromism). PTO shows three isosbestic points at 333, 388 and 472 nm in a binary mixture of acetone and chloroform. The deprotonation constants of PTO were found to be 3.1 and 5.8, based on spectrophotometric calculations. PTO was successfully used as an acid-base indicator; the acid solution color sharply turned from pink (acidic medium) to yellow (basic medium) at the end point.

The glmS Ribozyme Cofactor is a General Acid-Base Catalyst

PubMed Central

Viladoms, Julia; Fedor, Martha J.

2012-01-01

The glmS ribozyme is the first natural self-cleaving ribozyme known to require a cofactor. The D-glucosamine-6-phosphate (GlcN6P) cofactor has been proposed to serve as a general acid, but its role in the catalytic mechanism has not been established conclusively. We surveyed GlcN6P-like molecules for their ability to support self-cleavage of the glmS ribozyme and found a strong correlation between the pH dependence of the cleavage reaction and the intrinsic acidity of the cofactors. For cofactors with low binding affinities the contribution to rate enhancement was proportional to their intrinsic acidity. This linear free-energy relationship between cofactor efficiency and acid dissociation constants is consistent with a mechanism in which the cofactors participate directly in the reaction as general acid-base catalysts. A high value for the Brønsted coefficient (β ~ 0.7) indicates that a significant amount of proton transfer has already occurred in the transition state. The glmS ribozyme is the first self-cleaving RNA to use an exogenous acid-base catalyst. PMID:23113700

The glmS ribozyme cofactor is a general acid-base catalyst.

PubMed

Viladoms, Júlia; Fedor, Martha J

2012-11-21

The glmS ribozyme is the first natural self-cleaving ribozyme known to require a cofactor. The d-glucosamine-6-phosphate (GlcN6P) cofactor has been proposed to serve as a general acid, but its role in the catalytic mechanism has not been established conclusively. We surveyed GlcN6P-like molecules for their ability to support self-cleavage of the glmS ribozyme and found a strong correlation between the pH dependence of the cleavage reaction and the intrinsic acidity of the cofactors. For cofactors with low binding affinities, the contribution to rate enhancement was proportional to their intrinsic acidity. This linear free-energy relationship between cofactor efficiency and acid dissociation constants is consistent with a mechanism in which the cofactors participate directly in the reaction as general acid-base catalysts. A high value for the Brønsted coefficient (β ~ 0.7) indicates that a significant amount of proton transfer has already occurred in the transition state. The glmS ribozyme is the first self-cleaving RNA to use an exogenous acid-base catalyst.

Selective Chemical Conversion of Sugars in Aqueous Solutions without Alkali to Lactic Acid Over a Zn-Sn-Beta Lewis Acid-Base Catalyst

PubMed Central

Dong, Wenjie; Shen, Zheng; Peng, Boyu; Gu, Minyan; Zhou, Xuefei; Xiang, Bo; Zhang, Yalei

2016-01-01

Lactic acid is an important platform molecule in the synthesis of a wide range of chemicals. However, in aqueous solutions without alkali, its efficient preparation via the direct catalysis of sugars is hindered by a side dehydration reaction to 5-hydroxymethylfurfural due to Brønsted acid, which originates from organic acids. Herein, we report that a previously unappreciated combination of common two metal mixed catalyst (Zn-Sn-Beta) prepared via solid-state ion exchange synergistically promoted this reaction. In water without a base, a conversion exceeding 99% for sucrose with a lactic acid yield of 54% was achieved within 2 hours at 190 °C under ambient air pressure. Studies of the acid and base properties of the Zn-Sn-Beta zeolite suggest that the introduction of Zn into the Sn-Beta zeolite sequentially enhanced both the Lewis acid and base sites, and the base sites inhibited a series of side reactions related to fructose dehydration to 5-hydroxymethylfurfural and its subsequent decomposition. PMID:27222322

Weak Acid Ionization Constants and the Determination of Weak Acid-Weak Base Reaction Equilibrium Constants in the General Chemistry Laboratory

ERIC Educational Resources Information Center

Nyasulu, Frazier; McMills, Lauren; Barlag, Rebecca

2013-01-01

A laboratory to determine the equilibrium constants of weak acid negative weak base reactions is described. The equilibrium constants of component reactions when multiplied together equal the numerical value of the equilibrium constant of the summative reaction. The component reactions are weak acid ionization reactions, weak base hydrolysis…

Sodium butyrate epigenetically modulates high-fat diet-induced skeletal muscle mitochondrial adaptation, obesity and insulin resistance through nucleosome positioning

PubMed Central

Henagan, Tara M; Stefanska, Barbara; Fang, Zhide; Navard, Alexandra M; Ye, Jianping; Lenard, Natalie R; Devarshi, Prasad P

2015-01-01

Background and Purpose Sodium butyrate (NaB), an epigenetic modifier, is effective in promoting insulin sensitivity. The specific genomic loci and mechanisms underlying epigenetically induced obesity and insulin resistance and the targets of NaB are not fully understood. Experimental Approach The anti-diabetic and anti-obesity effects of NaB treatment were measured by comparing phenotypes and physiologies of C57BL/6J mice fed a low-fat diet (LF), high-fat diet (HF) or high-fat diet plus NaB (HF + NaB) for 10 weeks. We determined a possible mechanism of NaB action through induction of beneficial skeletal muscle mitochondrial adaptations and applied microccocal nuclease digestion with sequencing (MNase-seq) to assess whole genome differences in nucleosome occupancy or positioning and to identify associated epigenetic targets of NaB. Key Results NaB prevented HF diet-induced increases in body weight and adiposity without altering food intake or energy expenditure, improved insulin sensitivity as measured by glucose and insulin tolerance tests, and decreased respiratory exchange ratio. In skeletal muscle, NaB increased the percentage of type 1 fibres, improved acylcarnitine profiles as measured by metabolomics and produced a chromatin structure, determined by MNase-seq, similar to that seen in LF. Targeted analysis of representative nuclear-encoded mitochondrial genes showed specific repositioning of the −1 nucleosome in association with altered gene expression. Conclusions and Implications NaB treatment may be an effective pharmacological approach for type 2 diabetes and obesity by inducing −1 nucleosome repositioning within nuclear-encoded mitochondrial genes, causing skeletal muscle mitochondrial adaptations that result in more complete β-oxidation and a lean, insulin sensitive phenotype. PMID:25559882

Hexon and fiber of adenovirus type 14 and 55 are major targets of neutralizing antibody but only fiber-specific antibody contributes to cross-neutralizing activity.

PubMed

Feng, Ying; Sun, Xikui; Ye, Xianmiao; Feng, Yupeng; Wang, Jinlin; Zheng, Xuehua; Liu, Xinglong; Yi, Changhua; Hao, Mingli; Wang, Qian; Li, Feng; Xu, Wei; Li, Liang; Li, Chufang; Zhou, Rong; Chen, Ling; Feng, Liqiang

2018-05-01

Re-emerging human adenoviruses type 14 (HAdV14) and 55 (HAdV55) represent two highly virulent adenoviruses. The neutralizing antibody (nAb) responses elicited by infection or immunization remain largely unknown. Herein, we generated hexon-chimeric HAdV14 viruses harboring each single or entire hexon hyper-variable-regions (HVR) from HAdV55, and determined the neutralizing epitopes of human and mouse nAbs. In human sera, hexon-targeting nAbs are type-specific and mainly recognize HVR2, 5, and 7. Fiber-targeting nAbs are only detectable in sera cross-neutralizing HAdV14 and HAdV55 and contribute substantially to cross-neutralization. Penton-binding antibodies, however, show no significant neutralizing activities. In mice immunized with HAdV14 or HAdV55, a single immunization mainly elicited hexon-specific nAbs, which recognized HAdV14 HVR1, 2, and 7 and HAdV55 HVR1 and 2, respectively. After a booster immunization, cross-neutralizing fiber-specific nAbs became detectable. These results indicated that hexon elicits type-specific nAbs whereas fiber induces cross-neutralizing nAbs to HAdV14 and HAdV55, which are of significance in vaccine development. Copyright © 2018 Elsevier Inc. All rights reserved.

Pharmacokinetic and Pharmacodynamic Interaction of Andrographolide and Standardized Extract of Andrographis paniculata (Nees) with Nabumetone in Wistar Rats.

PubMed

Balap, Aishwarya; Lohidasan, Sathiyanarayanan; Sinnathambi, Arulmozhi; Mahadik, Kakasaheb

2017-01-01

The aim of the study was to investigate the herb-drug interaction of Andrographis paniculata Nees (Acanthaceae) and Andrographolide (AN) with nabumetone (NAB) in wistar rats. Pharmacokinetic and pharmacodynamic interactions were studied after co-administration of APE and AN with NAB in Wistar rats. In pharmacokinetic studies, significant decrease in Cmax, AUC 0-t and AUC 0-∞ of 6-MNA after co-administration with pure AN and APE has been observed. T max of 6-MNA has been increased to 2 h from 1.5 h in AN + NAB treated group. Changes in mean residential time, clearance and volume of distribution of 6-MNA in APE + NAB treated group and AN + NAB treated group indicated interference of other components of APE other than AN. In pharmacodynamic study, significant decrease in antiarthritic activity of NAB on concomitant administration with APE and AN has been observed. The study concludes that NAB exhibits pharmacokinetic and pharmacodynamic interactions with APE and AN in rats thus alarms the concomitant use of herbal preparations containing APE and AN with NAB. Further study is needed to understand the mechanism and predict the herb-drug interaction in humans. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Effect of temperature on the acid-base properties of the alumina surface: microcalorimetry and acid-base titration experiments.

PubMed

Morel, Jean-Pierre; Marmier, Nicolas; Hurel, Charlotte; Morel-Desrosiers, Nicole

2006-06-15

Sorption reactions on natural or synthetic materials that can attenuate the migration of pollutants in the geosphere could be affected by temperature variations. Nevertheless, most of the theoretical models describing sorption reactions are at 25 degrees C. To check these models at different temperatures, experimental data such as the enthalpies of sorption are thus required. Highly sensitive microcalorimeters can now be used to determine the heat effects accompanying the sorption of radionuclides on oxide-water interfaces, but enthalpies of sorption cannot be extracted from microcalorimetric data without a clear knowledge of the thermodynamics of protonation and deprotonation of the oxide surface. However, the values reported in the literature show large discrepancies and one must conclude that, amazingly, this fundamental problem of proton binding is not yet resolved. We have thus undertaken to measure by titration microcalorimetry the heat effects accompanying proton exchange at the alumina-water interface at 25 degrees C. Based on (i) the surface sites speciation provided by a surface complexation model (built from acid-base titrations at 25 degrees C) and (ii) results of the microcalorimetric experiments, calculations have been made to extract the enthalpic variations associated respectively to first and second deprotonation of the alumina surface. Values obtained are deltaH1 = 80+/-10 kJ mol(-1) and deltaH2 = 5+/-3 kJ mol(-1). In a second step, these enthalpy values were used to calculate the alumina surface acidity constants at 50 degrees C via the van't Hoff equation. Then a theoretical titration curve at 50 degrees C was calculated and compared to the experimental alumina surface titration curve. Good agreement between the predicted acid-base titration curve and the experimental one was observed.

Aspergillus oryzae-based cell factory for direct kojic acid production from cellulose.

PubMed

Yamada, Ryosuke; Yoshie, Toshihide; Wakai, Satoshi; Asai-Nakashima, Nanami; Okazaki, Fumiyoshi; Ogino, Chiaki; Hisada, Hiromoto; Tsutsumi, Hiroko; Hata, Yoji; Kondo, Akihiko

2014-05-18

Kojic acid (5-Hydroxy-2-(hydroxymethyl)-4-pyrone) is one of the major secondary metabolites in Aspergillus oryzae. It is widely used in food, pharmaceuticals, and cosmetics. The production cost, however, is too high for its use in many applications. Thus, an efficient and cost-effective kojic acid production process would be valuable. However, little is known about the complete set of genes for kojic acid production. Currently, kojic acid is produced from glucose. The efficient production of kojic acid using cellulose as an inexpensive substrate would help establish cost-effective kojic acid production. A kojic acid transcription factor gene over-expressing the A. oryzae strain was constructed. Three genes related to kojic acid production in this strain were transcribed in higher amounts than those found in the wild-type strain. This strain produced 26.4 g/L kojic acid from 80 g/L glucose. Furthermore, this strain was transformed with plasmid harboring 3 cellulase genes. The resultant A. oryzae strain successfully produced 0.18 g/L of kojic acid in 6 days of fermentation from the phosphoric acid swollen cellulose. Kojic acid was produced directly from cellulose material using genetically engineered A. oryzae. Because A. oryzae has efficient protein secretion ability and secondary metabolite productivity, an A. oryzae-based cell factory could be a platform for the production of various kinds of bio-based chemicals.

Nucleic and Amino Acid Sequences Support Structure-Based Viral Classification.

PubMed

Sinclair, Robert M; Ravantti, Janne J; Bamford, Dennis H

2017-04-15

Viral capsids ensure viral genome integrity by protecting the enclosed nucleic acids. Interactions between the genome and capsid and between individual capsid proteins (i.e., capsid architecture) are intimate and are expected to be characterized by strong evolutionary conservation. For this reason, a capsid structure-based viral classification has been proposed as a way to bring order to the viral universe. The seeming lack of sufficient sequence similarity to reproduce this classification has made it difficult to reject structural convergence as the basis for the classification. We reinvestigate whether the structure-based classification for viral coat proteins making icosahedral virus capsids is in fact supported by previously undetected sequence similarity. Since codon choices can influence nascent protein folding cotranslationally, we searched for both amino acid and nucleotide sequence similarity. To demonstrate the sensitivity of the approach, we identify a candidate gene for the pandoravirus capsid protein. We show that the structure-based classification is strongly supported by amino acid and also nucleotide sequence similarities, suggesting that the similarities are due to common descent. The correspondence between structure-based and sequence-based analyses of the same proteins shown here allow them to be used in future analyses of the relationship between linear sequence information and macromolecular function, as well as between linear sequence and protein folds. IMPORTANCE Viral capsids protect nucleic acid genomes, which in turn encode capsid proteins. This tight coupling of protein shell and nucleic acids, together with strong functional constraints on capsid protein folding and architecture, leads to the hypothesis that capsid protein-coding nucleotide sequences may retain signatures of ancient viral evolution. We have been able to show that this is indeed the case, using the major capsid proteins of viruses forming icosahedral capsids. Importantly

Nucleic and Amino Acid Sequences Support Structure-Based Viral Classification

PubMed Central

Sinclair, Robert M.; Ravantti, Janne J.

2017-01-01

ABSTRACT Viral capsids ensure viral genome integrity by protecting the enclosed nucleic acids. Interactions between the genome and capsid and between individual capsid proteins (i.e., capsid architecture) are intimate and are expected to be characterized by strong evolutionary conservation. For this reason, a capsid structure-based viral classification has been proposed as a way to bring order to the viral universe. The seeming lack of sufficient sequence similarity to reproduce this classification has made it difficult to reject structural convergence as the basis for the classification. We reinvestigate whether the structure-based classification for viral coat proteins making icosahedral virus capsids is in fact supported by previously undetected sequence similarity. Since codon choices can influence nascent protein folding cotranslationally, we searched for both amino acid and nucleotide sequence similarity. To demonstrate the sensitivity of the approach, we identify a candidate gene for the pandoravirus capsid protein. We show that the structure-based classification is strongly supported by amino acid and also nucleotide sequence similarities, suggesting that the similarities are due to common descent. The correspondence between structure-based and sequence-based analyses of the same proteins shown here allow them to be used in future analyses of the relationship between linear sequence information and macromolecular function, as well as between linear sequence and protein folds. IMPORTANCE Viral capsids protect nucleic acid genomes, which in turn encode capsid proteins. This tight coupling of protein shell and nucleic acids, together with strong functional constraints on capsid protein folding and architecture, leads to the hypothesis that capsid protein-coding nucleotide sequences may retain signatures of ancient viral evolution. We have been able to show that this is indeed the case, using the major capsid proteins of viruses forming icosahedral capsids

A Sensitive Gel-based Method Combining Distinct Cyclophellitol-based Probes for the Identification of Acid/Base Residues in Human Retaining β-Glucosidases*

PubMed Central

Kallemeijn, Wouter W.; Witte, Martin D.; Voorn-Brouwer, Tineke M.; Walvoort, Marthe T. C.; Li, Kah-Yee; Codée, Jeroen D. C.; van der Marel, Gijsbert A.; Boot, Rolf G.; Overkleeft, Herman S.; Aerts, Johannes M. F. G.

2014-01-01

Retaining β-exoglucosidases operate by a mechanism in which the key amino acids driving the glycosidic bond hydrolysis act as catalytic acid/base and nucleophile. Recently we designed two distinct classes of fluorescent cyclophellitol-type activity-based probes (ABPs) that exploit this mechanism to covalently modify the nucleophile of retaining β-glucosidases. Whereas β-epoxide ABPs require a protonated acid/base for irreversible inhibition of retaining β-glucosidases, β-aziridine ABPs do not. Here we describe a novel sensitive method to identify both catalytic residues of retaining β-glucosidases by the combined use of cyclophellitol β-epoxide- and β-aziridine ABPs. In this approach putative catalytic residues are first substituted to noncarboxylic amino acids such as glycine or glutamine through site-directed mutagenesis. Next, the acid/base and nucleophile can be identified via classical sodium azide-mediated rescue of mutants thereof. Selective labeling with fluorescent β-aziridine but not β-epoxide ABPs identifies the acid/base residue in mutagenized enzyme, as only the β-aziridine ABP can bind in its absence. The Absence of the nucleophile abolishes any ABP labeling. We validated the method by using the retaining β-glucosidase GBA (CAZy glycosylhydrolase family GH30) and then applied it to non-homologous (putative) retaining β-glucosidases categorized in GH1 and GH116: GBA2, GBA3, and LPH. The described method is highly sensitive, requiring only femtomoles (nanograms) of ABP-labeled enzymes. PMID:25344605

Replication Competent Molecular Clones of HIV-1 Expressing Renilla Luciferase Facilitate the Analysis of Antibody Inhibition in PBMC

PubMed Central

Edmonds, Tara G.; Ding, Haitao; Yuan, Xing; Wei, Qing; Smith, Kendra S.; Conway, Joan A.; Wieczorek, Lindsay; Brown, Bruce; Polonis, Victoria; West, John T.; Montefiori, David C.; Kappes, John C.; Ochsenbauer, Christina

2010-01-01

Effective vaccine development for human immunodeficiency virus type 1 (HIV-1) will require assays that ascertain the capacity of vaccine immunogens to elicit neutralizing antibodies (NAb) to diverse HIV-1 strains. To facilitate NAb assessment in peripheral blood mononuclear cell (PBMC)-based assays, we developed an assay-adaptable platform based on a Renilla luciferase (LucR) expressing HIV-1 proviral backbone. LucR was inserted into pNL4-3 DNA, preserving all viral open reading frames. The proviral genome was engineered to facilitate expression of diverse HIV-1 env sequences, allowing analysis in an isogenic background. The resulting Env-IMC-LucR viruses are infectious, and LucR is stably expressed over multiple replications in PBMC. HIV-1 neutralization, targeting TZM-bl cells, was highly correlative comparing virus (LucR) and cell (firefly luciferase) readouts. In PBMC, NAb activity can be analyzed either within a single or multiple cycles of replication. These results represent advancement toward a standardizable PBMC-based neutralization assay for assessing HIV-1 vaccine immunogen efficacy. PMID:20863545

Replication competent molecular clones of HIV-1 expressing Renilla luciferase facilitate the analysis of antibody inhibition in PBMC.

PubMed

Edmonds, Tara G; Ding, Haitao; Yuan, Xing; Wei, Qing; Smith, Kendra S; Conway, Joan A; Wieczorek, Lindsay; Brown, Bruce; Polonis, Victoria; West, John T; Montefiori, David C; Kappes, John C; Ochsenbauer, Christina

2010-12-05

Effective vaccine development for human immunodeficiency virus type 1 (HIV-1) will require assays that ascertain the capacity of vaccine immunogens to elicit neutralizing antibodies (NAb) to diverse HIV-1 strains. To facilitate NAb assessment in peripheral blood mononuclear cell (PBMC)-based assays, we developed an assay-adaptable platform based on a Renilla luciferase (LucR) expressing HIV-1 proviral backbone. LucR was inserted into pNL4-3 DNA, preserving all viral open reading frames. The proviral genome was engineered to facilitate expression of diverse HIV-1 env sequences, allowing analysis in an isogenic background. The resulting Env-IMC-LucR viruses are infectious, and LucR is stably expressed over multiple replications in PBMC. HIV-1 neutralization, targeting TZM-bl cells, was highly correlative comparing virus (LucR) and cell (firefly luciferase) readouts. In PBMC, NAb activity can be analyzed either within a single or multiple cycles of replication. These results represent advancement toward a standardizable PBMC-based neutralization assay for assessing HIV-1 vaccine immunogen efficacy. Copyright © 2010 Elsevier Inc. All rights reserved.

Oxalate Acid-Base Cements as a Means of Carbon Storage

NASA Astrophysics Data System (ADS)

Erdogan, S. T.

2017-12-01

Emission of CO2 from industrial processes poses a myriad of environmental problems. One such polluter is the portland cement (PC) industry. PC is the main ingredient in concrete which is the ubiquitous binding material for construction works. Its production is responsible for 5-10 % of all anthropogenic CO2 emissions. Half of this emission arises from the calcination of calcareous raw materials and half from kiln fuel burning and cement clinker grinding. There have long been efforts to reduce the carbon footprint of concrete. Among the many ways, one is to bind CO2 to the phases in the cement-water paste, oxides, hydroxides, and silicates of calcium, during early hydration or while in service. The problem is that obtaining calcium oxide cheaply requires the decarbonation of limestone and the uptake of CO2 is slow and limited mainly to the surface of the concrete due to its low gas permeability. Hence, a faster method to bind more CO2 is needed. Acid-base (AB) cements are fast-setting, high-strength systems that have high durability in many environments in which PC concrete is vulnerable. They are made with a powder base such as MgO and an acid or acid salt, like phosphates. Despite certain advantages over PC cement systems, AB cements are not feasible, due to their high acid content. Also, the phosphoric acid used comes from non-renewable sources of phosphate. A potential way to reduce the drawbacks of using phosphates could be to use organic acids. Oxalic acid or its salts could react with the proper powder base to give concrete that could be used for infrastructure hence that would have very high demand. In addition, methods to produce oxalates from CO2, even atmospheric, are becoming widespread and more economical. The base can also be an industrial byproduct to further lower the environmental impact. This study describes the use of oxalic acid and industrial byproducts to obtain mortars with mechanical properties comparable to those of PC mortars. It is

Antioxidative Categorization of Twenty Amino Acids Based on Experimental Evaluation.

PubMed

Xu, Naijin; Chen, Guanqun; Liu, Hui

2017-11-27

In view of the great importance bestowed on amino acids as antioxidants in oxidation resistance, we attempted two common redox titration methods in this report, including micro-potassium permanganate titration and iodometric titration, to measure the antioxidative capacity of 20 amino acids, which are the construction units of proteins in living organisms. Based on the relative intensities of the antioxidative capacity, we further conducted a quantitative comparison and found out that the product of experimental values obtained from the two methods was proven to be a better indicator for evaluating the relative antioxidative capacity of amino acids. The experimental results were largely in accordance with structural analysis made on amino acids. On the whole, the 20 amino acids concerned could be divided into two categories according to their antioxidative capacity. Seven amino acids, including tryptophan, methionine, histidine, lysine, cysteine, arginine and tyrosine, were greater in total antioxidative capacity compared with the other 13 amino acids.

New approach in the treatment of data from an acid-base potentiometric titrationI. Monocomponent systems of monofunctional acids and bases.

PubMed

Maslarska, Vania; Tencheva, Jasmina; Budevsky, Omortag

2003-01-01

Based on precise analysis of the acid-base equilibrium, a new approach in the treatment of experimental data from a potentiometric titration is proposed. A new general formula giving explicitly the relation V=f([H(+)]) is derived, valid for every acid-base titration, which includes mono- and polyfunctional protolytes and their mixtures. The present study is the first practical application of this formula for the simplest case, the analysis of one monofunctional protolyte. The collected mV data during the titration are converted into pH-values by means of an auto pH-calibration procedure, thus avoiding preliminary preparation of the measuring system. The mentioned pH-calibration method is applicable also in water-organic mixtures and allows the quantitative determination of sparingly soluble substances (particularly pharmaceuticals). The treatment of the data is performed by means of ready-to-use software products, which makes the proposed approach accessible for a wide range of applications.

Acid-base metabolism: implications for kidney stones formation.

PubMed

Hess, Bernhard

2006-04-01

The physiology and pathophysiology of renal H+ ion excretion and urinary buffer systems are reviewed. The main focus is on the two major conditions related to acid-base metabolism that cause kidney stone formation, i.e., distal renal tubular acidosis (dRTA) and abnormally low urine pH with subsequent uric acid stone formation. Both the entities can be seen on the background of disturbances of the major urinary buffer system, NH3+ <--> NH4+. On the one hand, reduced distal tubular secretion of H+ ions results in an abnormally high urinary pH and either incomplete or complete dRTA. On the other hand, reduced production/availability of NH4+ is the cause of an abnormally low urinary pH, which predisposes to uric acid stone formation. Most recent research indicates that the latter abnormality may be a renal manifestation of the increasingly prevalent metabolic syndrome. Despite opposite deviations from normal urinary pH values, both the dRTA and uric acid stone formation due to low urinary pH require the same treatment, i.e., alkali. In the dRTA, alkali is needed for improving the body's buffer capacity, whereas the goal of alkali treatment in uric acid stone formers is to increase the urinary pH to 6.2-6.8 in order to minimize uric acid crystallization.

Using Conceptual Change Texts with Analogies for Misconceptions in Acids and Bases

ERIC Educational Resources Information Center

Cetingul, Ipek; Geban, Omer

2011-01-01

This study was conducted to explore the effectiveness of conceptual change oriented instruction over traditional instruction on students' understanding of acids and bases concept. Besides, effects of gender difference and science process skills on students' understanding of acids and bases were also investigated. Analysis of the results showed…

Phytochemistry of cimicifugic acids and associated bases in Cimicifuga racemosa root extracts.

PubMed

Gödecke, Tanja; Nikolic, Dejan; Lankin, David C; Chen, Shao-Nong; Powell, Sharla L; Dietz, Birgit; Bolton, Judy L; van Breemen, Richard B; Farnsworth, Norman R; Pauli, Guido F

2009-01-01

Earlier studies reported serotonergic activity for cimicifugic acids (CA) isolated from Cimicifuga racemosa. The discovery of strongly basic alkaloids, cimipronidines, from the active extract partition and evaluation of previously employed work-up procedures has led to the hypothesis of strong acid/base association in the extract. Re-isolation of the CAs was desired to permit further detailed studies. Based on the acid/base association hypothesis, a new separation scheme of the active partition was required, which separates acids from associated bases. A new 5-HT(7) bioassay guided work-up procedure was developed that concentrates activity into one partition. The latter was subjected to a new two-step centrifugal partitioning chromatography (CPC) method, which applies pH zone refinement gradient (pHZR CPC) to dissociate the acid/base complexes. The resulting CA fraction was subjected to a second CPC step. Fractions and compounds were monitored by (1)H NMR using a structure-based spin-pattern analysis facilitating dereplication of the known acids. Bioassay results were obtained for the pHZR CPC fractions and for purified CAs. A new CA was characterised. While none of the pure CAs was active, the serotonergic activity was concentrated in a single pHZR CPC fraction, which was subsequently shown to contain low levels of the potent 5-HT(7) ligand, N(omega)-methylserotonin. This study shows that CAs are not responsible for serotonergic activity in black cohosh. New phytochemical methodology (pHZR CPC) and a sensitive dereplication method (LC-MS) led to the identification of N(omega)-methylserotonin as serotonergic active principle. Copyright (c) 2009 John Wiley & Sons, Ltd.

Phytochemistry of Cimicifugic Acids and Associated Bases in Cimicifuga racemosa Root Extracts

PubMed Central

GÖdecke, Tanja; Nikolic, Dejan; Lankin, David C.; Chen, Shao-Nong; Powell, Sharla L.; Dietz, Birgit; Bolton, Judy L.; Van Breemen, Richard B.; Farnsworth, Norman R.; Pauli, Guido F.

2009-01-01

Introduction Earlier studies reported serotonergic activity for cimicifugic acids (CA) isolated from Cimicifuga racemosa. The discovery of strongly basic alkaloids, cimipronidines, from the active extract partition and evaluation of previously employed work-up procedures has led to the hypothesis of strong acid/base association in the extract. Objective Re-isolation of the CAs was desired to permit further detailed studies. Based on the acid/base association hypothesis, a new separation scheme of the active partition was required, which separates acids from associated bases. Methodology A new 5-HT7 bioassay guided work-up procedure was developed that concentrates activity into one partition. The latter was subjected to a new 2-step centrifugal partitioning chromatography (CPC) method, which applies pH zone refinement gradient (pHZR CPC) to dissociate the acid/base complexes. The resulting CA fraction was subjected to a second CPC step. Fractions and compounds were monitored by 1H NMR using a structure based spin-pattern analysis facilitating dereplication of the known acids. Bioassay results were obtained for the pHZR CPC fractions and for purified CAs. Results A new CA was characterized. While none of the pure CAs was active, the serotonergic activity was concentrated in a single pHZR CPC fraction, which was subsequently shown to contain low levels of the potent 5-HT7 ligand, Nω–methylserotonin. Conclusion This study shows that CAs are not responsible for serotonergic activity in black cohosh. New phytochemical methodology (pHZR CPC) and a sensitive dereplication method (LC-MS) led to the identification of Nω–methylserotonin as serotonergic active principle. PMID:19140115

Equivalence-point electromigration acid-base titration via moving neutralization boundary electrophoresis.

PubMed

Yang, Qing; Fan, Liu-Yin; Huang, Shan-Sheng; Zhang, Wei; Cao, Cheng-Xi

2011-04-01

In this paper, we developed a novel method of acid-base titration, viz. the electromigration acid-base titration (EABT), via a moving neutralization boundary (MNR). With HCl and NaOH as the model strong acid and base, respectively, we conducted the experiments on the EABT via the method of moving neutralization boundary for the first time. The experiments revealed that (i) the concentration of agarose gel, the voltage used and the content of background electrolyte (KCl) had evident influence on the boundary movement; (ii) the movement length was a function of the running time under the constant acid and base concentrations; and (iii) there was a good linearity between the length and natural logarithmic concentration of HCl under the optimized conditions, and the linearity could be used to detect the concentration of acid. The experiments further manifested that (i) the RSD values of intra-day and inter-day runs were less than 1.59 and 3.76%, respectively, indicating similar precision and stability in capillary electrophoresis or HPLC; (ii) the indicators with different pK(a) values had no obvious effect on EABT, distinguishing strong influence on the judgment of equivalence-point titration in the classic one; and (iii) the constant equivalence-point titration always existed in the EABT, rather than the classic volumetric analysis. Additionally, the EABT could be put to good use for the determination of actual acid concentrations. The experimental results achieved herein showed a new general guidance for the development of classic volumetric analysis and element (e.g. nitrogen) content analysis in protein chemistry. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Closed cycle ion exchange method for regenerating acids, bases and salts

DOEpatents

Dreyfuss, Robert M.

1976-01-01

A method for conducting a chemical reaction in acidic, basic, or neutral solution as required and then regenerating the acid, base, or salt by means of ion exchange in a closed cycle reaction sequence which comprises contacting the spent acid, base, or salt with an ion exchanger, preferably a synthetic organic ion-exchange resin, so selected that the counter ions thereof are ions also produced as a by-product in the closed reaction cycle, and then regenerating the spent ion exchanger by contact with the by-product counter ions. The method is particularly applicable to closed cycle processes for the thermochemical production of hydrogen.

Aspergillus oryzae-based cell factory for direct kojic acid production from cellulose

PubMed Central

2014-01-01

Background Kojic acid (5-Hydroxy-2-(hydroxymethyl)-4-pyrone) is one of the major secondary metabolites in Aspergillus oryzae. It is widely used in food, pharmaceuticals, and cosmetics. The production cost, however, is too high for its use in many applications. Thus, an efficient and cost-effective kojic acid production process would be valuable. However, little is known about the complete set of genes for kojic acid production. Currently, kojic acid is produced from glucose. The efficient production of kojic acid using cellulose as an inexpensive substrate would help establish cost-effective kojic acid production. Results A kojic acid transcription factor gene over-expressing the A. oryzae strain was constructed. Three genes related to kojic acid production in this strain were transcribed in higher amounts than those found in the wild-type strain. This strain produced 26.4 g/L kojic acid from 80 g/L glucose. Furthermore, this strain was transformed with plasmid harboring 3 cellulase genes. The resultant A. oryzae strain successfully produced 0.18 g/L of kojic acid in 6 days of fermentation from the phosphoric acid swollen cellulose. Conclusions Kojic acid was produced directly from cellulose material using genetically engineered A. oryzae. Because A. oryzae has efficient protein secretion ability and secondary metabolite productivity, an A. oryzae-based cell factory could be a platform for the production of various kinds of bio-based chemicals. PMID:24885968

Intrasubtype B HIV-1 Superinfection Correlates with Delayed Neutralizing Antibody Response

PubMed Central

Landais, Elise; Caballero, Gemma; Phung, Pham; Kosakovsky Pond, Sergei L.; Poignard, Pascal; Richman, Douglas D.; Little, Susan J.; Smith, Davey M.

2017-01-01

ABSTRACT Understanding whether the neutralizing antibody (NAb) response impacts HIV-1 superinfection and how superinfection subsequently modulates the NAb response can help clarify correlates of protection from HIV exposures and better delineate pathways of NAb development. We examined associations between the development of NAb and the occurrence of superinfection in a well-characterized, antiretroviral therapy (ART)-naive, primary infection cohort of men who have sex with men. Deep sequencing was applied to blood plasma samples from the cohort to detect cases of superinfection. We compared the NAb activity against autologous and heterologous viruses between 10 participants with intrasubtype B superinfection and 19 monoinfected controls, matched to duration of infection and risk behavior. Three to 6 months after primary infection, individuals who would later become superinfected had significantly weaker NAb activity against tier 1 subtype B viruses (P = 0.003 for SF-162 and P = 0.017 for NL4-3) and marginally against autologous virus (P = 0.054). Lower presuperinfection NAb responses correlated with weaker gp120 binding and lower plasma total IgG titers. Soon after superinfection, the NAb response remained lower, but between 2 and 3 years after primary infection, NAb levels strengthened and reached those of controls. Superinfecting viruses were typically not susceptible to neutralization by presuperinfection plasma. These observations suggest that recently infected individuals with a delayed NAb response against primary infecting and tier 1 subtype B viruses are more susceptible to superinfection. IMPORTANCE Our findings suggest that within the first year after HIV infection, a relatively weak neutralizing antibody response against primary and subtype-specific neutralization-sensitive viruses increases susceptibility to superinfection in the face of repeated exposures. As natural infection progresses, the immune response strengthens significantly in some

Ventricular assist device elicits serum natural IgG that correlates with the development of primary graft dysfunction following heart transplantation.

PubMed

See, Sarah B; Clerkin, Kevin J; Kennel, Peter J; Zhang, Feifan; Weber, Matthew P; Rogers, Kortney J; Chatterjee, Debanjana; Vasilescu, Elena R; Vlad, George; Naka, Yoshifumi; Restaino, Susan W; Farr, Maryjane A; Topkara, Veli K; Colombo, Paolo C; Mancini, Donna M; Schulze, P Christian; Levin, Bruce; Zorn, Emmanuel

2017-08-01

Pre-transplant sensitization is a limiting factor in solid-organ transplantation. In heart transplants, ventricular assist device (VAD) implantation has been associated with sensitization to human leukocyte antigens (HLA). The effect of VAD on non-HLA antibodies is unclear. We have previously shown that polyreactive natural antibodies (Nabs) contribute to pre-sensitization in kidney allograft recipients. Here we assessed generation of Nabs after VAD implantation in pre-transplant sera and examined their contribution to cardiac allograft outcome. IgM and IgG Nabs were tested in pre-transplant serum samples collected from 206 orthotopic heart transplant recipients, including 128 patients with VAD (VAD patients) and 78 patients without VAD (no-VAD patients). Nabs were assessed by testing serum reactivity to apoptotic cells by flow cytometry and to the generic oxidized epitope, malondialdehyde, by enzyme-linked immunosorbent assay. No difference was observed in serum levels of IgM Nabs between VAD and no-VAD patients. However, serum IgG Nabs levels were significantly increased in VAD compared with no-VAD patients. This increase was likely due to the presence of the VAD, as revealed by lower serum IgG Nabs levels before implantation. Elevated pre-transplant IgG Nabs level was associated with development of primary graft dysfunction (PGD). Our study demonstrates that VAD support elicits IgG Nabs reactive to apoptotic cells and oxidized epitopes. These findings further support broad and non-specific B-cell activation by VAD, resulting in IgG sensitization. Moreover, the association of serum IgG Nabs levels with development of PGD suggests a possible role for these antibodies in the inflammatory reaction accompanying this complication. Copyright © 2017 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Intrasubtype B HIV-1 Superinfection Correlates with Delayed Neutralizing Antibody Response.

PubMed

Wagner, Gabriel A; Landais, Elise; Caballero, Gemma; Phung, Pham; Kosakovsky Pond, Sergei L; Poignard, Pascal; Richman, Douglas D; Little, Susan J; Smith, Davey M

2017-09-01

Understanding whether the neutralizing antibody (NAb) response impacts HIV-1 superinfection and how superinfection subsequently modulates the NAb response can help clarify correlates of protection from HIV exposures and better delineate pathways of NAb development. We examined associations between the development of NAb and the occurrence of superinfection in a well-characterized, antiretroviral therapy (ART)-naive, primary infection cohort of men who have sex with men. Deep sequencing was applied to blood plasma samples from the cohort to detect cases of superinfection. We compared the NAb activity against autologous and heterologous viruses between 10 participants with intrasubtype B superinfection and 19 monoinfected controls, matched to duration of infection and risk behavior. Three to 6 months after primary infection, individuals who would later become superinfected had significantly weaker NAb activity against tier 1 subtype B viruses ( P = 0.003 for SF-162 and P = 0.017 for NL4-3) and marginally against autologous virus ( P = 0.054). Lower presuperinfection NAb responses correlated with weaker gp120 binding and lower plasma total IgG titers. Soon after superinfection, the NAb response remained lower, but between 2 and 3 years after primary infection, NAb levels strengthened and reached those of controls. Superinfecting viruses were typically not susceptible to neutralization by presuperinfection plasma. These observations suggest that recently infected individuals with a delayed NAb response against primary infecting and tier 1 subtype B viruses are more susceptible to superinfection. IMPORTANCE Our findings suggest that within the first year after HIV infection, a relatively weak neutralizing antibody response against primary and subtype-specific neutralization-sensitive viruses increases susceptibility to superinfection in the face of repeated exposures. As natural infection progresses, the immune response strengthens significantly in some superinfected

Extra-epitopic hepatitis C virus polymorphisms confer resistance to broadly neutralizing antibodies by modulating binding to scavenger receptor B1.

PubMed

El-Diwany, Ramy; Cohen, Valerie J; Mankowski, Madeleine C; Wasilewski, Lisa N; Brady, Jillian K; Snider, Anna E; Osburn, William O; Murrell, Ben; Ray, Stuart C; Bailey, Justin R

2017-02-01

Broadly-neutralizing monoclonal antibodies (bNAbs) may guide vaccine development for highly variable viruses including hepatitis C virus (HCV), since they target conserved viral epitopes that could serve as vaccine antigens. However, HCV resistance to bNAbs could reduce the efficacy of a vaccine. HC33.4 and AR4A are two of the most potent anti-HCV human bNAbs characterized to date, binding to highly conserved epitopes near the amino- and carboxy-terminus of HCV envelope (E2) protein, respectively. Given their distinct epitopes, it was surprising that these bNAbs showed similar neutralization profiles across a panel of natural HCV isolates, suggesting that some viral polymorphisms may confer resistance to both bNAbs. To investigate this resistance, we developed a large, diverse panel of natural HCV envelope variants and a novel computational method to identify bNAb resistance polymorphisms in envelope proteins (E1 and E2). By measuring neutralization of a panel of HCV pseudoparticles by 10 μg/mL of each bNAb, we identified E1E2 variants with resistance to one or both bNAbs, despite 100% conservation of the AR4A binding epitope across the panel. We discovered polymorphisms outside of either binding epitope that modulate resistance to both bNAbs by altering E2 binding to the HCV co-receptor, scavenger receptor B1 (SR-B1). This study is focused on a mode of neutralization escape not addressed by conventional analysis of epitope conservation, highlighting the contribution of extra-epitopic polymorphisms to bNAb resistance and presenting a novel mechanism by which HCV might persist even in the face of an antibody response targeting multiple conserved epitopes.

Surface modification of polyisobutylene via grafting amino acid-based poly (acryloyl-6-aminocaproic acid) as multifunctional material.

PubMed

Du, Yanqiu; Li, Chunming; Jin, Jing; Li, Chao; Jiang, Wei

2018-01-01

Amino acid-based P(acryloyl-6-aminocaproic acid) (PAACA) brushes were fabricated on polyisobutylene (PIB) surface combined with plasma pre-treatment and UV-induced grafting polymerization to construct an antifouling and functional material. The hydrophilicity and hemocompatibility of PIB were largely improved by surface modification of AACA, which were confirmed by water contact angle and platelet adhesion, respectively. PAACA brushes were precisely located onto the surface of PIB to create a patterned PIB-g-PAACA structure, and then the carboxyl groups on PAACA was activated to immobilize functional protein-Concanavalin A (Con A). The obtained Con A-coupled microdomains could further capture erythrocytes. This method developed a platform on commercial PIB surface via amino acid-based polymer brushes which had a promising application in drug delivery and disease diagnosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Amino acid-based surfactants – do they deserve more attention?

PubMed

Bordes, Romain; Holmberg, Krister

2015-08-01

The 20 standard amino acids (together with a few more that are not used in the biosynthesis of proteins) constitute a versatile tool box for synthesis of surfactants. Anionic, cationic and zwitterionic amphiphiles can be prepared and surfactants with several functional groups can be obtained by the proper choice of starting amino acid. This review gives examples of procedures used for preparation and discusses important physicochemical properties of the amphiphiles and how these can be taken advantage of for various applications. Micelles with a chiral surface can be obtained by self-assembly of enantiomerically pure surfactants and such supramolecular chirality can be utilized for asymmetric organic synthesis and for preparation of mesoporous materials with chiral pores. Surfactants based on amino acids with two carboxyl groups are effective chelating agents and can be used as collectors in mineral ore flotation. A surfactant based on cysteine readily oxidizes into the corresponding cystine compound, which can be regarded as a gemini surfactant. The facile and reversible cysteine-cystine transformation has been taken advantage of in the design of a switchable surfactant. A very attractive aspect of surfactants based on amino acids is that the polar head-group is entirely natural and that the linkage to the hydrophobic tail, which is often an ester or an amide bond, is easily cleaved. The rate of degradation can be tailored by the structure of the amphiphile. The ester linkage in betaine ester surfactants is particularly susceptible to alkaline hydrolysis and this surfactant type can be used as a biocide with short-lived action. This paper is not intended as a full review on the topic. Instead it highlights concepts that are unique to amino acid-based surfactants and that we believe can have practical implications. Copyright © 2015 Elsevier B.V. All rights reserved.

Acid and base stress and transcriptomic responses in Bacillus subtilis.

PubMed

Wilks, Jessica C; Kitko, Ryan D; Cleeton, Sarah H; Lee, Grace E; Ugwu, Chinagozi S; Jones, Brian D; BonDurant, Sandra S; Slonczewski, Joan L

2009-02-01

Acid and base environmental stress responses were investigated in Bacillus subtilis. B. subtilis AG174 cultures in buffered potassium-modified Luria broth were switched from pH 8.5 to pH 6.0 and recovered growth rapidly, whereas cultures switched from pH 6.0 to pH 8.5 showed a long lag time. Log-phase cultures at pH 6.0 survived 60 to 100% at pH 4.5, whereas cells grown at pH 7.0 survived <15%. Cells grown at pH 9.0 survived 40 to 100% at pH 10, whereas cells grown at pH 7.0 survived <5%. Thus, growth in a moderate acid or base induced adaptation to a more extreme acid or base, respectively. Expression indices from Affymetrix chip hybridization were obtained for 4,095 protein-encoding open reading frames of B. subtilis grown at external pH 6, pH 7, and pH 9. Growth at pH 6 upregulated acetoin production (alsDS), dehydrogenases (adhA, ald, fdhD, and gabD), and decarboxylases (psd and speA). Acid upregulated malate metabolism (maeN), metal export (czcDO and cadA), oxidative stress (catalase katA; OYE family namA), and the SigX extracytoplasmic stress regulon. Growth at pH 9 upregulated arginine catabolism (roc), which generates organic acids, glutamate synthase (gltAB), polyamine acetylation and transport (blt), the K(+)/H(+) antiporter (yhaTU), and cytochrome oxidoreductases (cyd, ctaACE, and qcrC). The SigH, SigL, and SigW regulons were upregulated at high pH. Overall, greater genetic adaptation was seen at pH 9 than at pH 6, which may explain the lag time required for growth shift to high pH. Low external pH favored dehydrogenases and decarboxylases that may consume acids and generate basic amines, whereas high external pH favored catabolism-generating acids.

Using the Logarithmic Concentration Diagram, Log "C", to Teach Acid-Base Equilibrium

ERIC Educational Resources Information Center

Kovac, Jeffrey

2012-01-01

Acid-base equilibrium is one of the most important and most challenging topics in a typical general chemistry course. This article introduces an alternative to the algebraic approach generally used in textbooks, the graphical log "C" method. Log "C" diagrams provide conceptual insight into the behavior of aqueous acid-base systems and allow…

Acid-Base Properties of Azo Dyes in Solution Studied Using Spectrophotometry and Colorimetry

NASA Astrophysics Data System (ADS)

Snigur, D. V.; Chebotarev, A. N.; Bevziuk, K. V.

2018-03-01

Colorimetry and spectrophotometry with chemometric data processing were used to study the acid-base properties of azo dyes in aqueous solution. The capabilities of both methods were compared. Ionization constants of all the functional groups of the azo compounds studied could be determined relative to the change in the specific color difference depending on the acidity of the medium. The colorimetric functions of ion-molecular forms of azo compounds used as an analytical signal allow us to obtain complete information on the acid-base equilibrium in a wide acidity range.

Serum IFN neutralizing antibodies and neopterin levels in a cross-section of MS patients.

PubMed

Cook, S D; Quinless, J R; Jotkowitz, A; Beaton, P

2001-09-25

To determine levels of serum interferon beta (IFNbeta) neutralizing antibody (NAb) and neopterin-an IFN biologic response marker-in patients with MS treated with Betaseron or Avonex. Controversy exists over the relative immunogenicity of IFNbeta-1a and IFNbeta-1b and the reasons for any such difference. To determine the role of patient profile and test methodology in IFNbeta, NAb levels need to be measured blindly and simultaneously in a predefined closely matched MS patient cohort. Serum NAb and neopterin levels were measured in closely matched patients on Avonex (n = 98) or Betaseron (n = 64). NAb were determined by Athena Diagnostics and serum neopterin levels by Covance Laboratories using a competitive binding radioimmunoassay. More patients taking Betaseron (22%) than Avonex (7%) had elevated titers of NAb (p = 0.008). Mean serum neopterin levels were lower in patients with high as compared to low NAb titers (p = 0.0002). No difference in mean neopterin levels was found comparing the total Betaseron group to the Avonex group; however, in the subset of patients with low NAb titers, mean neopterin levels were higher in the Betaseron than in the Avonex group (p = 0.027). A random cross-sectional sampling of patients on Avonex showed a decrease in neopterin levels over time between weekly doses. NAb are more commonly found with Betaseron than Avonex. More studies are needed to determine the correlation among serum neopterin levels, other biologic response markers, NAb, and disease activity in patients with MS being treated with IFNbeta.

Electrolyte and Acid-Base Disturbances in End-Stage Liver Disease: A Physiopathological Approach.

PubMed

Jiménez, José Víctor; Carrillo-Pérez, Diego Luis; Rosado-Canto, Rodrigo; García-Juárez, Ignacio; Torre, Aldo; Kershenobich, David; Carrillo-Maravilla, Eduardo

2017-08-01

Electrolyte and acid-base disturbances are frequent in patients with end-stage liver disease; the underlying physiopathological mechanisms are often complex and represent a diagnostic and therapeutic challenge to the physician. Usually, these disorders do not develop in compensated cirrhotic patients, but with the onset of the classic complications of cirrhosis such as ascites, renal failure, spontaneous bacterial peritonitis and variceal bleeding, multiple electrolyte, and acid-base disturbances emerge. Hyponatremia parallels ascites formation and is a well-known trigger of hepatic encephalopathy; its management in this particular population poses a risky challenge due to the high susceptibility of cirrhotic patients to osmotic demyelination. Hypokalemia is common in the setting of cirrhosis: multiple potassium wasting mechanisms both inherent to the disease and resulting from its management make these patients particularly susceptible to potassium depletion even in the setting of normokalemia. Acid-base disturbances range from classical respiratory alkalosis to high anion gap metabolic acidosis, almost comprising the full acid-base spectrum. Because most electrolyte and acid-base disturbances are managed in terms of their underlying trigger factors, a systematic physiopathological approach to their diagnosis and treatment is required.

Using Spreadsheets to Produce Acid-Base Titration Curves.

ERIC Educational Resources Information Center

Cawley, Martin James; Parkinson, John

1995-01-01

Describes two spreadsheets for producing acid-base titration curves, one uses relatively simple cell formulae that can be written into the spreadsheet by inexperienced students and the second uses more complex formulae that are best written by the teacher. (JRH)

2-Keto acids based biosynthesis pathways for renewable fuels and chemicals.

PubMed

Tashiro, Yohei; Rodriguez, Gabriel M; Atsumi, Shota

2015-03-01

Global energy and environmental concerns have driven the development of biological chemical production from renewable sources. Biological processes using microorganisms are efficient and have been traditionally utilized to convert biomass (i.e., glucose) to useful chemicals such as amino acids. To produce desired fuels and chemicals with high yield and rate, metabolic pathways have been enhanced and expanded with metabolic engineering and synthetic biology approaches. 2-Keto acids, which are key intermediates in amino acid biosynthesis, can be converted to a wide range of chemicals. 2-Keto acid pathways were engineered in previous research efforts and these studies demonstrated that 2-keto acid pathways have high potential for novel metabolic routes with high productivity. In this review, we discuss recently developed 2-keto acid-based pathways.

Neurologic complications of electrolyte disturbances and acid-base balance.

PubMed

Espay, Alberto J

2014-01-01

Electrolyte and acid-base disturbances are common occurrences in daily clinical practice. Although these abnormalities can be readily ascertained from routine laboratory findings, only specific clinical correlates may attest as to their significance. Among a wide phenotypic spectrum, acute electrolyte and acid-base disturbances may affect the peripheral nervous system as arreflexic weakness (hypermagnesemia, hyperkalemia, and hypophosphatemia), the central nervous system as epileptic encephalopathies (hypomagnesemia, dysnatremias, and hypocalcemia), or both as a mixture of encephalopathy and weakness or paresthesias (hypocalcemia, alkalosis). Disabling complications may develop not only when these derangements are overlooked and left untreated (e.g., visual loss from intracranial hypertension in respiratory or metabolic acidosis; quadriplegia with respiratory insufficiency in hypermagnesemia) but also when they are inappropriately managed (e.g., central pontine myelinolisis when rapidly correcting hyponatremia; cardiac arrhythmias when aggressively correcting hypo- or hyperkalemia). Therefore prompt identification of the specific neurometabolic syndromes is critical to correct the causative electrolyte or acid-base disturbances and prevent permanent central or peripheral nervous system injury. This chapter reviews the pathophysiology, clinical investigations, clinical phenotypes, and current management strategies in disorders resulting from alterations in the plasma concentration of sodium, potassium, calcium, magnesium, and phosphorus as well as from acidemia and alkalemia. © 2014 Elsevier B.V. All rights reserved.

Exposure to histone deacetylase inhibitors during Pavlovian conditioning enhances subsequent cue-induced reinstatement of operant behavior.

PubMed

Ploense, Kyle L; Kerstetter, Kerry A; Wade, Matthew A; Woodward, Nicholas C; Maliniak, Dan; Reyes, Michael; Uchizono, Russell S; Bredy, Timothy W; Kippin, Tod E

2013-06-01

Histone deacetylase inhibitors (HDACIs) strengthen memory following fear conditioning and cocaine-induced conditioned place preference. Here, we examined the effects of two nonspecific HDACIs, valproic acid (VPA) and sodium butyrate (NaB), on appetitive learning measured by conditioned stimulus (CS)-induced reinstatement of operant responding. Rats were trained to lever press for food reinforcement and then injected with VPA (50-200 mg/kg, i.p.), NaB (250-1000 mg/kg, i.p.), or saline vehicle (1.0 ml/kg), 2 h before receiving pairings of noncontingent presentation of food pellets preceded by a tone+light cue CS. Rats next underwent extinction of operant responding followed by response-contingent re-exposure to the CS. Rats receiving VPA (100 mg/kg) or NaB (1000 mg/kg) before conditioning displayed significantly higher cue-induced reinstatement than did saline controls. Rats that received either vehicle or VPA (100 mg/kg) before a conditioning session with a randomized relation between presentation of food pellets and the CS failed to show subsequent cue-induced reinstatement with no difference between the two groups. These findings indicate that, under certain contexts, HDACIs strengthen memory formation by specifically increasing the associative strength of the CS, not through an increasing motivation to seek reinforcement. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Exposure to histone deacetylase inhibitors during Pavlovian conditioning enhances subsequent cue-induced reinstatement of operant behavior

PubMed Central

Ploense, Kyle L.; Kerstetter, Kerry A.; Wade, Matthew A.; Woodward, Nicholas C.; Maliniak, Dan; Reyes, Michael; Uchizono, Russell S.; Bredy, Timothy W.; Kippin, Tod E.

2014-01-01

Histone deacetylase inhibitors (HDACIs) strengthen memory following fear conditioning and cocaine-induced conditioned place preference. Here, we examined the effects of two non-specific HDACIs, valproic acid (VPA) and sodium butyrate (NaB), on appetitive learning measured via conditioned stimulus (CS)-induced reinstatement of operant responding. Rats were trained to lever press for food reinforcement and then injected with VPA (50–200 mg/kg, i.p.), NaB (250–1000 mg/kg, i.p.), or saline vehicle (1.0 ml/kg), 2h before receiving pairings of noncontingent presentation of food pellets preceded by a tone+light cue CS. Rats next underwent extinction of operant responding followed by response-contingent re-exposure to the CS. Rats receiving VPA (100 mg/kg) or NaB (1000 mg/kg) prior to conditioning displayed significantly higher cue-induced reinstatement than did saline controls. Rats that receiving either vehicle or VPA (100 mg/kg) prior to a conditioning session with a randomized relation between presentation of food pellets and the CS failed to show subsequent cue-induced reinstatement with no difference between the two groups. These findings indicate that, under certain contexts, HDACIs strengthen memory formation by specifically increasing the associative strength of the CS, not through an increasing motivation to seek reinforcement. PMID:23604166

Top value platform chemicals: bio-based production of organic acids.

PubMed

Becker, Judith; Lange, Anna; Fabarius, Jonathan; Wittmann, Christoph

2015-12-01

Driven by the quest for sustainability, recent years have seen a tremendous progress in bio-based production routes from renewable raw materials to commercial goods. Particularly, the production of organic acids has crystallized as a competitive and fast-evolving field, related to the broad applicability of organic acids for direct use, as polymer building blocks, and as commodity chemicals. Here, we review recent advances in metabolic engineering and industrial market scenarios with focus on organic acids as top value products from biomass, accessible through fermentation and biotransformation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Separation of Acids, Bases, and Neutral Compounds

NASA Astrophysics Data System (ADS)

Fujita, Megumi; Mah, Helen M.; Sgarbi, Paulo W. M.; Lall, Manjinder S.; Ly, Tai Wei; Browne, Lois M.

2003-01-01

Separation of Acids, Bases, and Neutral Compounds requires the following software, which is available for free download from the Internet: Netscape Navigator, version 4.75 or higher, or Microsoft Internet Explorer, version 5.0 or higher; Chime plug-in, version compatible with your OS and browser (available from MDL); and Flash player, version 5 or higher (available from Macromedia).

Red Shoe-Blue Shoe: An Acid-Base Demonstration with a Fashionable Twist.

ERIC Educational Resources Information Center

Breyer, Arthur C.; Uzelmeier, Calvin E.

1998-01-01

Illustrates that acid-base indicators come in many forms and the reversible effects that acids and bases have on the colors of such indicators. An object is dyed in an indicator, which causes the object to turn dark blue at pH less than 3.0 to 5.0. Suggests using dyeable fabric shoes and other cotton articles. (PVD)

Studies on acid-base status (Stewart's model) of young camels (Camelus dromedarius) after acid-load with NH4Cl.

PubMed

Elkhair, Nawal M; Hartmann, Helmut

2010-01-01

The identification of the reference values of Stewart variables and the changes in the acid-base status of the blood and urine in relation to the age after acid-load were studied in desert species of camels. 14 healthy young camels (age: 3-5 months) and 22 adult camels (age: 5-8 years) were used to provide the reference and percentile ranges of the Stewart variables. In the experiments, 24 healthy young camels (age: < 3-5 months) were infused with 5M NH4Cl solution (dose: 1.0 ml/kg) through a permanent intravenous catheter. Venous blood and urine samples were collected before infusion (0 hours). After the start of infusion, venous blood samples were collected at 2, 4, 6, 8 and 24 hours, and urine samples were collected at 8, 24 and 48 hours. Blood and urine samples were used for the determination of the various acid-base parameters, including the non-respiratory Stewart variables. The reference range of serum-[strong ion difference = SID3] was 39-52 mmol/l for all age groups. The reference values of serum-[acid total = A-] were between 10-17 mmol/l for all age groups. Serum-[Atotprotein] and -[Atot-albumin] showed a reference range of 19-24 mmol/I and 20-28 mmol/l, respectively. By 2-8 hours after the NH4Cl-load, the Stewart variables (serum-[SID3] and serum-[A(tot-protein)]) decreased significantly, and as a consequence, the blood pH decreased. Generally, the loaded young camels showed a transient moderate hyperchloraemic acidosis with a slight hypoproteinaemic alkalosis. These malfunctions were accompanied by increased renal fractional excretion of chloride and sodium and decreased urine pH. The identified reference values of the Stewart variables can be used for the clinical diagnosis of acid-base disturbances in camels. With the assistance of the non-respiratory Stewart variables ([SID3] and [Atot]), we can detect the determining influence of strong electrolytes (Na+, K+ and Cl-) and weak acids (proteins, Pi) on the physiological and pathological acid-base

A digital image-based method for determining of total acidity in red wines using acid-base titration without indicator.

PubMed

Tôrres, Adamastor Rodrigues; Lyra, Wellington da Silva; de Andrade, Stéfani Iury Evangelista; Andrade, Renato Allan Navarro; da Silva, Edvan Cirino; Araújo, Mário César Ugulino; Gaião, Edvaldo da Nóbrega

2011-05-15

This work proposes the use of digital image-based method for determination of total acidity in red wines by means of acid-base titration without using an external indicator or any pre-treatment of the sample. Digital images present the colour of the emergent radiation which is complementary to the radiation absorbed by anthocyanines present in wines. Anthocyanines change colour depending on the pH of the medium, and from the variation of colour in the images obtained during titration, the end point can be localized with accuracy and precision. RGB-based values were employed to build titration curves, and end points were localized by second derivative curves. The official method recommends potentiometric titration with a NaOH standard solution, and sample dilution until the pH reaches 8.2-8.4. In order to illustrate the feasibility of the proposed method, titrations of ten red wines were carried out. Results were compared with the reference method, and no statistically significant difference was observed between the results by applying the paired t-test at the 95% confidence level. The proposed method yielded more precise results than the official method. This is due to the trivariate nature of the measurements (RGB), associated with digital images. Copyright © 2011 Elsevier B.V. All rights reserved.

Bicarbonate sensing in mouse cortical astrocytes during extracellular acid/base disturbances.

PubMed

Theparambil, Shefeeq M; Naoshin, Zinnia; Defren, Sabrina; Schmaelzle, Jana; Weber, Tobias; Schneider, Hans-Peter; Deitmer, Joachim W

2017-04-15

The present study suggests that the electrogenic sodium-bicarbonate cotransporter, NBCe1, supported by carbonic anhydrase II, CAII, provides an efficient mechanism of bicarbonate sensing in cortical astrocytes. This mechanism is proposed to play a major role in setting the pH i responses to extracellular acid/base challenges in astrocytes. A decrease in extracellular [HCO 3 - ] during isocapnic acidosis and isohydric hypocapnia, or an increase in intracellular [HCO 3 - ] during hypercapnic acidosis, was effectively sensed by NBCe1, which carried bicarbonate out of the cells under these conditions, and caused an acidification and sodium fall in WT astrocytes, but not in NBCe1-knockout astrocytes. Isocapnic acidosis, hypercapnic acidosis and isohydric hypocapnia evoked inward currents in NBCe1- and CAII-expressing Xenopus laevis oocytes, but not in native oocytes, suggesting that NBCe1 operates in the outwardly directed mode under these conditions consistent with our findings in astrocytes. We propose that bicarbonate sensing of astrocytes may have functional significance during extracellular acid/base disturbances in the brain, as it not only alters intracellular pH/[HCO 3 - ]-dependent functions of astrocytes, but also modulates the extracellular pH/[HCO 3 - ] in brain tissue. Extracellular acid/base status of the mammalian brain undergoes dynamic changes during many physiological and pathological events. Although intracellular pH (pH i ) of astrocytes responds to extracellular acid/base changes, the mechanisms mediating these changes have remained unresolved. We have previously shown that the electrogenic sodium-bicarbonate cotransporter, NBCe1, is a high-affinity bicarbonate carrier in cortical astrocytes. In the present study, we investigated whether NBCe1 plays a role in bicarbonate sensing in astrocytes, and in determining the pH i responses to extracellular acid/base challenges. We measured changes in intracellular H + and Na + in astrocytes from wild

Bicarbonate sensing in mouse cortical astrocytes during extracellular acid/base disturbances

PubMed Central

Naoshin, Zinnia; Defren, Sabrina; Schmaelzle, Jana; Weber, Tobias; Schneider, Hans‐Peter

2017-01-01

Key points The present study suggests that the electrogenic sodium–bicarbonate cotransporter, NBCe1, supported by carbonic anhydrase II, CAII, provides an efficient mechanism of bicarbonate sensing in cortical astrocytes. This mechanism is proposed to play a major role in setting the pHi responses to extracellular acid/base challenges in astrocytes.A decrease in extracellular [HCO3 −] during isocapnic acidosis and isohydric hypocapnia, or an increase in intracellular [HCO3 −] during hypercapnic acidosis, was effectively sensed by NBCe1, which carried bicarbonate out of the cells under these conditions, and caused an acidification and sodium fall in WT astrocytes, but not in NBCe1‐knockout astrocytes.Isocapnic acidosis, hypercapnic acidosis and isohydric hypocapnia evoked inward currents in NBCe1‐ and CAII‐expressing Xenopus laevis oocytes, but not in native oocytes, suggesting that NBCe1 operates in the outwardly directed mode under these conditions consistent with our findings in astrocytes.We propose that bicarbonate sensing of astrocytes may have functional significance during extracellular acid/base disturbances in the brain, as it not only alters intracellular pH/[HCO3 −]‐dependent functions of astrocytes, but also modulates the extracellular pH/[HCO3 −] in brain tissue. Abstract Extracellular acid/base status of the mammalian brain undergoes dynamic changes during many physiological and pathological events. Although intracellular pH (pHi) of astrocytes responds to extracellular acid/base changes, the mechanisms mediating these changes have remained unresolved. We have previously shown that the electrogenic sodium–bicarbonate cotransporter, NBCe1, is a high‐affinity bicarbonate carrier in cortical astrocytes. In the present study, we investigated whether NBCe1 plays a role in bicarbonate sensing in astrocytes, and in determining the pHi responses to extracellular acid/base challenges. We measured changes in intracellular H+ and Na+ in

Murine Antibody Responses to Cleaved Soluble HIV-1 Envelope Trimers Are Highly Restricted in Specificity

PubMed Central

Hu, Joyce K.; Crampton, Jordan C.; Cupo, Albert; Ketas, Thomas; van Gils, Marit J.; Sliepen, Kwinten; de Taeye, Steven W.; Sok, Devin; Ozorowski, Gabriel; Deresa, Isaiah; Stanfield, Robyn; Ward, Andrew B.; Burton, Dennis R.; Klasse, Per Johan; Sanders, Rogier W.; Moore, John P.

2015-01-01

ABSTRACT Generating neutralizing antibodies (nAbs) is a major goal of many current HIV-1 vaccine efforts. To be of practical value, these nAbs must be both potent and cross-reactive in order to be capable of preventing the transmission of the highly diverse and generally neutralization resistant (Tier-2) HIV-1 strains that are in circulation. The HIV-1 envelope glycoprotein (Env) spike is the only target for nAbs. To explore whether Tier-2 nAbs can be induced by Env proteins, we immunized conventional mice with soluble BG505 SOSIP.664 trimers that mimic the native Env spike. Here, we report that it is extremely difficult for murine B cells to recognize the Env epitopes necessary for inducing Tier-2 nAbs. Thus, while trimer-immunized mice raised Env-binding IgG Abs and had high-quality T follicular helper (Tfh) cell and germinal center (GC) responses, they did not make BG505.T332N nAbs. Epitope mapping studies showed that Ab responses in mice were specific to areas near the base of the soluble trimer. These areas are not well shielded by glycans and likely are occluded on virions, which is consistent with the lack of BG505.T332N nAbs. These data inform immunogen design and suggest that it is useful to obscure nonneutralizing epitopes presented on the base of soluble Env trimers and that the glycan shield of well-formed HIV Env trimers is virtually impenetrable for murine B cell receptors (BCRs). IMPORTANCE Human HIV vaccine efficacy trials have not generated meaningful neutralizing antibodies to circulating HIV strains. One possible hindrance has been the lack of immunogens that properly mimic the native conformation of the HIV envelope trimer protein. Here, we tested the first generation of soluble, native-like envelope trimer immunogens in a conventional mouse model. We attempted to generate neutralizing antibodies to neutralization-resistant circulating HIV strains. Various vaccine strategies failed to induce neutralizing antibodies to a neutralization

Assessing Visuospatial Skills in Parkinson's: Comparison of Neuropsychological Assessment Battery Visual Discrimination to the Judgment of Line Orientation.

PubMed

Renfroe, Jenna B; Turner, Travis H; Hinson, Vanessa K

2017-02-01

Judgment of Line Orientation (JOLO) test is widely used in assessing visuospatial deficits in Parkinson's disease (PD). The neuropsychological assessment battery (NAB) offers the Visual Discrimination test, with age and education correction, parallel forms, and co-normed standardization sample for comparisons within and between domains. However, NAB Visual Discrimination has not been validated in PD, and may not measure the same construct as JOLO. A heterogeneous sample of 47 PD patients completed the JOLO and NAB Visual Discrimination within a broader neuropsychological evaluation. Pearson correlations assessed relationships between JOLO and NAB Visual Discrimination performances. Raw and demographically corrected scores from JOLO and Visual Discrimination were only weakly correlated. NAB Visual Discrimination subtest was moderately correlated with overall cognitive functioning, whereas the JOLO was not. Despite apparent virtues, results do not support NAB Visual Discrimination as an alternative to JOLO in assessing visuospatial functioning in PD. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Conformational Plasticity in Broadly Neutralizing HIV-1 Antibodies Triggers Polyreactivity.

PubMed

Prigent, Julie; Jarossay, Annaëlle; Planchais, Cyril; Eden, Caroline; Dufloo, Jérémy; Kök, Ayrin; Lorin, Valérie; Vratskikh, Oxana; Couderc, Thérèse; Bruel, Timothée; Schwartz, Olivier; Seaman, Michael S; Ohlenschläger, Oliver; Dimitrov, Jordan D; Mouquet, Hugo

2018-05-29

Human high-affinity antibodies to pathogens often recognize unrelated ligands. The molecular origin and the role of this polyreactivity are largely unknown. Here, we report that HIV-1 broadly neutralizing antibodies (bNAbs) are frequently polyreactive, cross-reacting with non-HIV-1 molecules, including self-antigens. Mutating bNAb genes to increase HIV-1 binding and neutralization also results in de novo polyreactivity. Unliganded paratopes of polyreactive bNAbs with improved HIV-1 neutralization exhibit a conformational flexibility, which contributes to enhanced affinity of bNAbs to various HIV-1 envelope glycoproteins and non-HIV antigens. Binding adaptation of polyreactive bNAbs to the divergent ligands mainly involves hydrophophic interactions. Plasticity of bNAbs' paratopes may, therefore, facilitate accommodating divergent viral variants, but it simultaneously triggers promiscuous binding to non-HIV-1 antigens. Thus, a certain level of polyreactivity can be a mark of adaptable antibodies displaying optimal pathogens' recognition. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Bifunctional Organic Polymeric Catalysts with a Tunable Acid-Base Distance and Framework Flexibility

PubMed Central

Chen, Huanhui; Wang, Yanan; Wang, Qunlong; Li, Junhui; Yang, Shiqi; Zhu, Zhirong

2014-01-01

Acid-base bifunctional organic polymeric catalysts were synthesized with tunable structures. we demonstrated two synthesis approaches for structural fine-tune. In the first case, the framework flexibility was tuned by changing the ratio of rigid blocks to flexible blocks within the polymer framework. In the second case, we precisely adjusted the acid-base distance by distributing basic monomers to be adjacent to acidic monomers, and by changing the chain length of acidic monomers. In a standard test reaction for the aldol condensation of 4-nitrobenzaldehyde with acetone, the catalysts showed good reusability upon recycling and maintained relatively high conversion percentage. PMID:25267260

Soil Studies: Applying Acid-Base Chemistry to Environmental Analysis.

ERIC Educational Resources Information Center

West, Donna M.; Sterling, Donna R.

2001-01-01

Laboratory activities for chemistry students focus attention on the use of acid-base chemistry to examine environmental conditions. After using standard laboratory procedures to analyze soil and rainwater samples, students use web-based resources to interpret their findings. Uses CBL probes and graphing calculators to gather and analyze data and…

Development of Cefotaxime Impregnated Chitosan as Nano-antibiotics: De Novo Strategy to Combat Biofilm Forming Multi-drug Resistant Pathogens

PubMed Central

Jamil, Bushra; Habib, Huma; Abbasi, Shahid A.; Ihsan, Ayesha; Nasir, Habib; Imran, Muhammad

2016-01-01

Frequent incidents of antibiotic-resistant biofilm forming pathogens in community-associated and hospital-acquired infections have become a global concern owing to failure of conventional therapies. Nano-antibiotics (NABs) are de novo tools to overcome the multi-drug resistant mechanisms employed by the superbugs. Inhibition of biofilm formation is one of those strategies to curb multi drug resistance phenomenon. In the current study, the anti-biofilm and antibacterial potential of newly synthesized cefotaxime loaded chitosan based NABs have been investigated. Both bare and cefotaxime loaded NABs were prepared by ionotropic gelation method. They were found carrying positive zeta potential of more than +50 mV, indicating highly stable nano-dispersion. Moreover, microscopic studies revealed their size as less than 100 nm. NABs were tested against clinical isolates of multi drug resistant Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, and methicillin resistant Staphylococcus aureus and wherein they demonstrated broad-spectrum anti-biofilm and anti-pathogenic activity. Thus, in vitro synergistic action of cephalosporin drugs and chitosan polymer at nano-scale in contrast to free antibiotics can be an improved broad-spectrum strategy to thwart resistance mechanisms in both Gram-positive and Gram-negative resistant pathogens. PMID:27047457

Influence of dissolved organic carbon content on modelling natural organic matter acid-base properties.

PubMed

Garnier, Cédric; Mounier, Stéphane; Benaïm, Jean Yves

2004-10-01

Natural organic matter (NOM) behaviour towards proton is an important parameter to understand NOM fate in the environment. Moreover, it is necessary to determine NOM acid-base properties before investigating trace metals complexation by natural organic matter. This work focuses on the possibility to determine these acid-base properties by accurate and simple titrations, even at low organic matter concentrations. So, the experiments were conducted on concentrated and diluted solutions of extracted humic and fulvic acid from Laurentian River, on concentrated and diluted model solutions of well-known simple molecules (acetic and phenolic acids), and on natural samples from the Seine river (France) which are not pre-concentrated. Titration experiments were modelled by a 6 acidic-sites discrete model, except for the model solutions. The modelling software used, called PROSECE (Programme d'Optimisation et de SpEciation Chimique dans l'Environnement), has been developed in our laboratory, is based on the mass balance equilibrium resolution. The results obtained on extracted organic matter and model solutions point out a threshold value for a confident determination of the studied organic matter acid-base properties. They also show an aberrant decreasing carboxylic/phenolic ratio with increasing sample dilution. This shift is neither due to any conformational effect, since it is also observed on model solutions, nor to ionic strength variations which is controlled during all experiments. On the other hand, it could be the result of an electrode troubleshooting occurring at basic pH values, which effect is amplified at low total concentration of acidic sites. So, in our conditions, the limit for a correct modelling of NOM acid-base properties is defined as 0.04 meq of total analysed acidic sites concentration. As for the analysed natural samples, due to their high acidic sites content, it is possible to model their behaviour despite the low organic carbon concentration.

A review of the different techniques for solid surface acid-base characterization.

PubMed

Sun, Chenhang; Berg, John C

2003-09-18

In this work, various techniques for solid surface acid-base (AB) characterization are reviewed. Different techniques employ different scales to rank acid-base properties. Based on the results from literature and the authors' own investigations for mineral oxides, these scales are compared. The comparison shows that Isoelectric Point (IEP), the most commonly used AB scale, is not a description of the absolute basicity or acidity of a surface, but a description of their relative strength. That is, a high IEP surface shows more basic functionality comparing with its acidic functionality, whereas a low IEP surface shows less basic functionality comparing with its acidic functionality. The choice of technique and scale for AB characterization depends on the specific application. For the cases in which the overall AB property is of interest, IEP (by electrokinetic titration) and H(0,max) (by indicator dye adsorption) are appropriate. For the cases in which the absolute AB property is of interest such as in the study of adhesion, it is more pertinent to use chemical shift (by XPS) and the heat of adsorption of probe gases (by calorimetry or IGC).

HIV-specific Fc effector function early in infection predicts the development of broadly neutralizing antibodies.

PubMed

Richardson, Simone I; Chung, Amy W; Natarajan, Harini; Mabvakure, Batsirai; Mkhize, Nonhlanhla N; Garrett, Nigel; Abdool Karim, Salim; Moore, Penny L; Ackerman, Margaret E; Alter, Galit; Morris, Lynn

2018-04-01

While the induction of broadly neutralizing antibodies (bNAbs) is a major goal of HIV vaccination strategies, there is mounting evidence to suggest that antibodies with Fc effector function also contribute to protection against HIV infection. Here we investigated Fc effector functionality of HIV-specific IgG plasma antibodies over 3 years of infection in 23 individuals, 13 of whom developed bNAbs. Antibody-dependent cellular phagocytosis (ADCP), complement deposition (ADCD), cellular cytotoxicity (ADCC) and cellular trogocytosis (ADCT) were detected in almost all individuals with levels of activity increasing over time. At 6 months post-infection, individuals with bNAbs had significantly higher levels of ADCD and ADCT that correlated with antibody binding to C1q and FcγRIIa respectively. In addition, antibodies from individuals with bNAbs showed more IgG subclass diversity to multiple HIV antigens which also correlated with Fc polyfunctionality. Germinal center activity represented by CXCL13 levels and expression of activation-induced cytidine deaminase (AID) was found to be associated with neutralization breadth, Fc polyfunctionality and IgG subclass diversity. Overall, multivariate analysis by random forest classification was able to group bNAb individuals with 85% sensitivity and 80% specificity based on the properties of their antibody Fc early in HIV infection. Thus, the Fc effector function profile predicted the development of neutralization breadth in this cohort, suggesting that intrinsic immune factors within the germinal center provide a mechanistic link between the Fc and Fab of HIV-specific antibodies.

Photochemistry of nucleic acid bases and their thio- and aza-analogues in solution.

PubMed

Pollum, Marvin; Martínez-Fernández, Lara; Crespo-Hernández, Carlos E

2015-01-01

The steady-state and time-resolved photochemistry of the natural nucleic acid bases and their sulfur- and nitrogen-substituted analogues in solution is reviewed. Emphasis is given to the experimental studies performed over the last 3-5 years that showcase topical areas of scientific inquiry and those that require further scrutiny. Significant progress has been made toward mapping the radiative and nonradiative decay pathways of nucleic acid bases. There is a consensus that ultrafast internal conversion to the ground state is the primary relaxation pathway in the nucleic acid bases, whereas the mechanism of this relaxation and the level of participation of the (1)πσ*, (1) nπ*, and (3)ππ* states are still matters of debate. Although impressive research has been performed in recent years, the microscopic mechanism(s) by which the nucleic acid bases dissipate excess vibrational energy to their environment, and the role of the N-glycosidic group in this and in other nonradiative decay pathways, are still poorly understood. The simple replacement of a single atom in a nucleobase with a sulfur or nitrogen atom severely restricts access to the conical intersections responsible for the intrinsic internal conversion pathways to the ground state in the nucleic acid bases. It also enhances access to ultrafast and efficient inter-system crossing pathways that populate the triplet manifold in yields close to unity. Determining the coupled nuclear and electronic pathways responsible for the significantly different photochemistry in these nucleic acid base analogues serves as a convenient platform to examine the current state of knowledge regarding the photodynamic properties of the DNA and RNA bases from both experimental and computational perspectives. Further investigations should also aid in forecasting the prospective use of sulfur- and nitrogen-substituted base analogues in photochemotherapeutic applications.

Poly(ethylene glycol) (PEG)-lactic acid nanocarrier-based degradable hydrogels for restoring the vaginal microenvironment

PubMed Central

Rajan, Sujata Sundara; Turovskiy, Yevgeniy; Singh, Yashveer; Chikindas, Michael L.; Sinko, Patrick J.

2014-01-01

Women with bacterial vaginosis (BV) display reduced vaginal acidity, which make them susceptible to associated infections such as HIV. In the current study, poly(ethylene glycol) (PEG) nanocarrier-based degradable hydrogels were developed for the controlled release of lactic acid in the vagina of BV-infected women. PEG-lactic acid (PEG-LA) nanocarriers were prepared by covalently attaching lactic acid to 8-arm PEG-SH via cleavable thioester bonds. PEG-LA nanocarriers with 4 copies of lactic acid per molecule provided controlled release of lactic acid with a maximum release of 23% and 47% bound lactic acid in phosphate buffered saline (PBS, pH 7.4) and acetate buffer (AB, pH 4.3), respectively. The PEG nanocarrier-based hydrogels were formed by cross-linking the PEG-LA nanocarriers with 4-arm PEG-NHS via degradable thioester bonds. The nanocarrier-based hydrogels formed within 20 min under ambient conditions and exhibited an elastic modulus that was 100-fold higher than the viscous modulus. The nanocarrier-based degradable hydrogels provided controlled release of lactic acid for several hours; however, a maximum release of only 10%–14% bound lactic acid was observed possibly due to steric hindrance of the polymer chains in the cross-linked hydrogel. In contrast, hydrogels with passively entrapped lactic acid showed burst release with complete release within 30 min. Lactic acid showed antimicrobial activity against the primary BV pathogen Gardnerella vaginalis with a minimum inhibitory concentration (MIC) of 3.6 mg/ml. In addition, the hydrogels with passively entrapped lactic acid showed retained antimicrobial activity with complete inhibition G. vaginalis growth within 48 h. The results of the current study collectively demonstrate the potential of PEG nanocarrier-based hydrogels for vaginal administration of lactic acid for preventing and treating BV. PMID:25223229

Electrolyte diodes with weak acids and bases. I. Theory and an approximate analytical solution.

PubMed

Iván, Kristóf; Simon, Péter L; Wittmann, Mária; Noszticzius, Zoltán

2005-10-22

Until now acid-base diodes and transistors applied strong mineral acids and bases exclusively. In this work properties of electrolyte diodes with weak electrolytes are studied and compared with those of diodes with strong ones to show the advantages of weak acids and bases in these applications. The theoretical model is a one dimensional piece of gel containing fixed ionizable groups and connecting reservoirs of an acid and a base. The electric current flowing through the gel is measured as a function of the applied voltage. The steady-state current-voltage characteristic (CVC) of such a gel looks like that of a diode under these conditions. Results of our theoretical, numerical, and experimental investigations are reported in two parts. In this first, theoretical part governing equations necessary to calculate the steady-state CVC of a reverse-biased electrolyte diode are presented together with an approximate analytical solution of this reaction-diffusion-ionic migration problem. The applied approximations are quasielectroneutrality and quasiequilibrium. It is shown that the gel can be divided into an alkaline and an acidic zone separated by a middle weakly acidic region. As a further approximation it is assumed that the ionization of the fixed acidic groups is complete in the alkaline zone and that it is completely suppressed in the acidic one. The general solution given here describes the CVC and the potential and ionic concentration profiles of diodes applying either strong or weak electrolytes. It is proven that previous formulas valid for a strong acid-strong base diode can be regarded as a special case of the more general formulas presented here.

Up-regulation of neurotrophic factors by cinnamon and its metabolite sodium benzoate: therapeutic implications for neurodegenerative disorders.

PubMed

Jana, Arundhati; Modi, Khushbu K; Roy, Avik; Anderson, John A; van Breemen, Richard B; Pahan, Kalipada

2013-06-01

This study underlines the importance of cinnamon, a widely-used food spice and flavoring material, and its metabolite sodium benzoate (NaB), a widely-used food preservative and a FDA-approved drug against urea cycle disorders in humans, in increasing the levels of neurotrophic factors [e.g., brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3)] in the CNS. NaB, but not sodium formate (NaFO), dose-dependently induced the expression of BDNF and NT-3 in primary human neurons and astrocytes. Interestingly, oral administration of ground cinnamon increased the level of NaB in serum and brain and upregulated the levels of these neurotrophic factors in vivo in mouse CNS. Accordingly, oral feeding of NaB, but not NaFO, also increased the level of these neurotrophic factors in vivo in the CNS of mice. NaB induced the activation of protein kinase A (PKA), but not protein kinase C (PKC), and H-89, an inhibitor of PKA, abrogated NaB-induced increase in neurotrophic factors. Furthermore, activation of cAMP response element binding (CREB) protein, but not NF-κB, by NaB, abrogation of NaB-induced expression of neurotrophic factors by siRNA knockdown of CREB and the recruitment of CREB and CREB-binding protein to the BDNF promoter by NaB suggest that NaB exerts its neurotrophic effect through the activation of CREB. Accordingly, cinnamon feeding also increased the activity of PKA and the level of phospho-CREB in vivo in the CNS. These results highlight a novel neutrophic property of cinnamon and its metabolite NaB via PKA - CREB pathway, which may be of benefit for various neurodegenerative disorders.

Effects of Sodium Butyrate on Methamphetamine-Sensitized Locomotor Activity

PubMed Central

Harkness, John H.; Hitzemann, Robert J.; Edmunds, Stephanie; Phillips, Tamara J.

2012-01-01

Neuroadaptations associated with behavioral sensitization induced by repeated exposure to methamphetamine (MA) appear to be involved in compulsive drug pursuit and use. Increased histone acetylation, an epigenetic effect resulting in altered gene expression, may promote sensitized responses to psychostimulants. The role of histone acetylation in the expression and acquisition of MA-induced locomotor sensitization was examined by measuring the effect of histone deacetylase inhibition by sodium butyrate (NaB). For the effect on expression, vehicle or NaB (630 mg/kg, intraperitoneally) was administered 30 min prior to MA challenge in mice treated repeatedly with MA (10 days of 2 mg/kg MA) or saline (10 days), and then locomotor response to MA challenge was measured. NaB treatment increased the locomotor response to MA in both acutely MA treated and sensitized animals. For acquisition, NaB was administered 30 min prior to each MA exposure (10 days of 1 or 2 mg/kg), but not prior to the MA challenge test. Treatment with NaB during the sensitization acquisition period significantly increased locomotor activation by MA in sensitized mice only. NaB alone did not significantly alter locomotor activity. Acute NaB or MA, but not the combination, appeared to increase striatal acetylation at histone H4. Repeated treatment with MA, but not NaB or MA plus NaB, increased striatal acetylation at histone H3. Although increased histone acetylation may alter the expression of genes involved in acute locomotor response to MA and in the acquisition of MA-induced sensitization, results for acetylation at H3 and H4 showed little correspondence with behavior. PMID:23137698

Trace analysis of acids and bases by conductometric titration with multiparametric non-linear regression.

PubMed

Coelho, Lúcia H G; Gutz, Ivano G R

2006-03-15

A chemometric method for analysis of conductometric titration data was introduced to extend its applicability to lower concentrations and more complex acid-base systems. Auxiliary pH measurements were made during the titration to assist the calculation of the distribution of protonable species on base of known or guessed equilibrium constants. Conductivity values of each ionized or ionizable species possibly present in the sample were introduced in a general equation where the only unknown parameters were the total concentrations of (conjugated) bases and of strong electrolytes not involved in acid-base equilibria. All these concentrations were adjusted by a multiparametric nonlinear regression (NLR) method, based on the Levenberg-Marquardt algorithm. This first conductometric titration method with NLR analysis (CT-NLR) was successfully applied to simulated conductometric titration data and to synthetic samples with multiple components at concentrations as low as those found in rainwater (approximately 10 micromol L(-1)). It was possible to resolve and quantify mixtures containing a strong acid, formic acid, acetic acid, ammonium ion, bicarbonate and inert electrolyte with accuracy of 5% or better.

Acid-base equilibrium in aqueous solutions of 1,3-dimethylbarbituric acid as studied by 13C NMR spectroscopy

NASA Astrophysics Data System (ADS)

Gryff-Keller, A.; Kraska-Dziadecka, A.

2011-12-01

13C NMR spectra of 1,3-dimethylbarbituric acid in aqueous solutions of various acidities and for various solute concentrations have been recorded and interpreted. The spectra recorded at pH = 2 and below contain the signals of the neutral solute molecule exclusively, while the ones recorded at pH = 7 and above only the signals of the appropriate anion, which has been confirmed by theoretical GIAO-DFT calculations. The signals in the spectra recorded for solutions of pH < 7 show dynamic broadenings. The lineshape analysis of these signals has provided information on the kinetics of the processes running in the dynamic acid-base equilibrium. The kinetic data determined this way have been used to clarify the mechanisms of these processes. The numerical analysis has shown that under the investigated conditions deprotonation of the neutral solute molecules undergoes not only via a simple transfer of the C-H proton to water molecules but also through a process with participation of the barbiturate anions. Moreover, the importance of tautomerism, or association, or both these phenomena for the kinetics of the acid-base transformations in the investigated system has been shown. Qualitatively similar changes of 13C NMR spectra with the solution pH variation have been observed for the parent barbituric acid.

Connecting Acids and Bases with Encapsulation... and Chemistry with Nanotechnology

ERIC Educational Resources Information Center

Criswell, Brett

2007-01-01

The features and the development of various new acids and bases activity sets that combines chemistry with nanotechnology are being described. These sets lead to the generation of many nanotechnology-based pharmaceuticals for the treatment of various diseases.

α-Ketoglutarate regulates acid-base balance through an intrarenal paracrine mechanism

PubMed Central

Tokonami, Natsuko; Morla, Luciana; Centeno, Gabriel; Mordasini, David; Ramakrishnan, Suresh Krishna; Nikolaeva, Svetlana; Wagner, Carsten A.; Bonny, Olivier; Houillier, Pascal; Doucet, Alain; Firsov, Dmitri

2013-01-01

Paracrine communication between different parts of the renal tubule is increasingly recognized as an important determinant of renal function. Previous studies have shown that changes in dietary acid-base load can reverse the direction of apical α-ketoglutarate (αKG) transport in the proximal tubule and Henle’s loop from reabsorption (acid load) to secretion (base load). Here we show that the resulting changes in the luminal concentrations of αKG are sensed by the αKG receptor OXGR1 expressed in the type B and non-A–non-B intercalated cells of the connecting tubule (CNT) and the cortical collecting duct (CCD). The addition of 1 mM αKG to the tubular lumen strongly stimulated Cl–-dependent HCO3– secretion and electroneutral transepithelial NaCl reabsorption in microperfused CCDs of wild-type mice but not Oxgr1–/– mice. Analysis of alkali-loaded mice revealed a significantly reduced ability of Oxgr1–/– mice to maintain acid-base balance. Collectively, these results demonstrate that OXGR1 is involved in the adaptive regulation of HCO3– secretion and NaCl reabsorption in the CNT/CCD under acid-base stress and establish αKG as a paracrine mediator involved in the functional coordination of the proximal and the distal parts of the renal tubule. PMID:23934124

Acid-base and electrolyte disorders in patients with diabetes mellitus.

PubMed

Sotirakopoulos, Nikolaos; Kalogiannidou, Irini; Tersi, Maria; Armentzioiou, Karmen; Sivridis, Dimitrios; Mavromatidis, Konstantinos

2012-01-01

Diabetes mellitus is the most common metabolic disorder in the community. The diabetics may suffer from acid-base and electrolyte disorders due to complications of diabetes mellitus and the medication they receive. In this study, acid-base and electrolyte disorders were evaluated among outpatient diabetics in our hospital. The study consisted of patients with diabetes mellitus who visited the hospital as outpatients between the period January 1, 2004 to December 31, 2006. The patients' medical history, age and type of diabetes were noted, including whether they were taking diuretics and calcium channel blockers or not. Serum creatinine, proteins, sodium, potassium and chloride and blood gases were measured in all patients. Proteinuria was measured by 24-h urine collection. Two hundred and ten patients were divided in three groups based on the serum creatinine. Group A consisted of 114 patients that had serum creatinine < 1.2 mg/dL, group B consisted of 69 patients that had serum creatinine ranging from 1.3 to 3 mg/dL and group C consisted of 27 patients with serum creatinine > 3.1 mg/dL. Of the 210 patients, 176 had an acid-base disorder. The most common disorder noted in group A was metabolic alkalosis. In groups B and C, the common disorders were metabolic acidosis and alkalosis, and metabolic acidosis, respectively. The most common electrolyte disorders were hypernatremia (especially in groups A and B), hyponatremia (group C) and hyperkalemia (especially in groups B and C). It is concluded that: (a) in diabetic outpatients, acid-base and electrolyte disorders occurred often even if the renal function is normal, (b) the most common disorders are metabolic alkalosis and metabolic acidosis (the frequency increases with the deterioration of the renal function) and (c) the common electrolyte disorders are hypernatremia and hypokalemia.

alpha-(Phenylazo)-4-nitrobenzyl cyanide, a new acid-base indicator.

PubMed

Légrádi, L

1970-02-01

A new acid-base indicator, alpha-(phenylazo)-4-nitrobenzyl cyanide, is proposed. The indicator changes colour from yellow to violet in the presence of alkali owing to the formation of a nitronic acid structure. This indicator is applicable for the titration of weak acids in acetone and ethanol media or in a mixture of these organic solvents and water, with 0.1M aqueous sodium hydroxide as titrant. The absorption spectra have been recorded for the indicator in 25%, 50% and 75% aqueous ethanol and acetone. By means of the spectra the dissociation constants in these media have been determined. The pK value of alpha-(phenylazo)-4-nitrobenzyl cyanide is 12.10 in water, and is decreased considerably in acetone but only slightly in ethanol. This behaviour is similar to that of positively charged weak acids and irregular for a weak acid carrying no charge or a negative charge.

Thioarsenides: A case for long-range Lewis acid-base-directed van der Waals interactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gibbs, Gerald V.; Wallace, Adam F.; Downs, R. T.

2011-04-01

Electron density distributions, bond paths, Laplacian and local energy density properties have been calculated for a number of As4Sn (n = 3,4,5) thioarsenide molecular crystals. On the basis of the distributions, the intramolecular As-S and As-As interactions classify as shared bonded interactions and the intermolecular As-S, As-As and S-S interactions classify as closed-shell van der Waals bonded interactions. The bulk of the intermolecular As-S bond paths link regions of locally concentrated electron density (Lewis base regions) with aligned regions of locally depleted electron density (Lewis acid regions) on adjacent molecules. The paths are comparable with intermolecular paths reported for severalmore » other molecular crystals that link aligned Lewis base and acid regions in a key-lock fashion, interactions that classified as long range Lewis acid-base directed van der Waals interactions. As the bulk of the intermolecular As-S bond paths (~70%) link Lewis acid-base regions on adjacent molecules, it appears that molecules adopt an arrangement that maximizes the number of As-S Lewis acid-base intermolecular bonded interactions. The maximization of the number of Lewis acid-base interactions appears to be connected with the close-packed array adopted by molecules: distorted cubic close-packed arrays are adopted for alacránite, pararealgar, uzonite, realgar and β-AsS and the distorted hexagonal close-packed arrays adopted by α- and β-dimorphite. A growth mechanism is proposed for thioarsenide molecular crystals from aqueous species that maximizes the number of long range Lewis acid-base vdW As-S bonded interactions with the resulting directed bond paths structuralizing the molecules as a molecular crystal.« less

Spectroscopic study on variations in illite surface properties after acid-base titration.

PubMed

Liu, Wen-xin; Coveney, R M; Tang, Hong-xiao

2003-07-01

FT-IR, Raman microscopy, XRD, 29Si and 27Al MAS NMR, were used to investigate changes in surface properties of a natural illite sample after acid-base potentiometric titration. The characteristic XRD lines indicated the presence of surface Al-Si complexes, preferable to Al(OH)3 precipitates. In the microscopic Raman spectra, the vibration peaks of Si-O and Al-O bonds diminished as a result of treatment with acid, then increased after hydroxide back titration. The varied ratio of signal intensity between (IV)Al and (VI)Al species in 27Al MAS NMR spectra, together with the stable BET surface area after acidimetric titration, suggested that edge faces and basal planes in the layer structure of illite participated in dissolution of structural components. The combined spectroscopic evidence demonstrated that the reactions between illite surfaces and acid-leaching silicic acid and aluminum ions should be considered in the model description of surface acid-base properties of the aqueous illite.

Determining surface areas of marine alga cells by acid-base titration method.

PubMed

Wang, X; Ma, Y; Su, Y

1997-09-01

A new method for determining the surface area of living marine alga cells was described. The method uses acid-base titration to measure the surface acid/base amount on the surface of alga cells and uses the BET (Brunauer, Emmett, and Teller) equation to estimate the maximum surface acid/base amount, assuming that hydrous cell walls have carbohydrates or other structural compounds which can behave like surface Brönsted acid-base sites due to coordination of environmental H2O molecules. The method was applied to 18 diverse alga species (including 7 diatoms, 2 flagellates, 8 green algae and 1 red alga) maintained in seawater cultures. For the species examined, the surface areas of individual cells ranged from 2.8 x 10(-8) m2 for Nannochloropsis oculata to 690 x 10(-8) m2 for Dunaliella viridis, specific surface areas from 1,030 m2.g-1 for Dunaliella salina to 28,900 m2.g-1 for Pyramidomonas sp. Measurement accuracy was 15.2%. Preliminary studies show that the method may be more promising and accurate than light/electron microscopic measurements for coarse estimation of the surface area of living algae.

Superabsorbent biphasic system based on poly(lactic acid) and poly(acrylic acid)

NASA Astrophysics Data System (ADS)

Sartore, Luciana; Pandini, Stefano; Baldi, Francesco; Bignotti, Fabio

2016-05-01

In this research work, biocomposites based on crosslinked particles of poly(acrylic acid), commonly used as superabsorbent polymer (SAP), and poly-L-lactic acid (PLLA) were developed to elucidate the role of the filler (i.e., polymeric crosslinked particles) on the overall physico-mechanical behavior and to obtain superabsorbent thermoplastic products. Samples prepared by melt-blending of components in different ratios showed a biphasic system with a regular distribution of particles, with diameter ranging from 5 to 10 μm, within the PLLA polymeric matrix. The polymeric biphasic system, coded PLASA i.e. superabsorbent poly(lactic acid), showed excellent swelling properties, demonstrating that cross-linked particles retain their superabsorbent ability, as in their free counterparts, even if distributed in a thermoplastic polymeric matrix. The thermal characteristics of the biocomposites evidence enhanced thermal stability in comparison with neat PLLA and also mechanical properties are markedly modified by addition of crosslinked particles which induce regular stiffening effect. Furthermore, in aqueous environments the particles swell and are leached from PLLA matrix generating very high porosity. These new open-pore PLLA foams, produced in absence of organic solvents and chemical foaming agents, with good physico-mechanical properties appear very promising for several applications, for instance in tissue engineering for scaffold production.

Stewart analysis of apparently normal acid-base state in the critically ill.

PubMed

Moviat, Miriam; van den Boogaard, Mark; Intven, Femke; van der Voort, Peter; van der Hoeven, Hans; Pickkers, Peter

2013-12-01

This study aimed to describe Stewart parameters in critically ill patients with an apparently normal acid-base state and to determine the incidence of mixed metabolic acid-base disorders in these patients. We conducted a prospective, observational multicenter study of 312 consecutive Dutch intensive care unit patients with normal pH (7.35 ≤ pH ≤ 7.45) on days 3 to 5. Apparent (SIDa) and effective strong ion difference (SIDe) and strong ion gap (SIG) were calculated from 3 consecutive arterial blood samples. Multivariate linear regression analysis was performed to analyze factors potentially associated with levels of SIDa and SIG. A total of 137 patients (44%) were identified with an apparently normal acid-base state (normal pH and -2 < base excess < 2 and 35 < PaCO2 < 45 mm Hg). In this group, SIDa values were 36.6 ± 3.6 mEq/L, resulting from hyperchloremia (109 ± 4.6 mEq/L, sodium-chloride difference 30.0 ± 3.6 mEq/L); SIDe values were 33.5 ± 2.3 mEq/L, resulting from hypoalbuminemia (24.0 ± 6.2 g/L); and SIG values were 3.1 ± 3.1 mEq/L. During admission, base excess increased secondary to a decrease in SIG levels and, subsequently, an increase in SIDa levels. Levels of SIDa were associated with positive cation load, chloride load, and admission SIDa (multivariate r(2) = 0.40, P < .001). Levels of SIG were associated with kidney function, sepsis, and SIG levels at intensive care unit admission (multivariate r(2) = 0.28, P < .001). Intensive care unit patients with an apparently normal acid-base state have an underlying mixed metabolic acid-base disorder characterized by acidifying effects of a low SIDa (caused by hyperchloremia) and high SIG combined with the alkalinizing effect of hypoalbuminemia. © 2013.

High School Students' Understanding of Acid-Base Concepts: An Ongoing Challenge for Teachers

ERIC Educational Resources Information Center

Damanhuri, Muhd Ibrahim Muhamad; Treagust, David F.; Won, Mihye; Chandrasegaran, A. L.

2016-01-01

Using a quantitative case study design, the "Acids-Bases Chemistry Achievement Test" ("ABCAT") was developed to evaluate the extent to which students in Malaysian secondary schools achieved the intended curriculum on acid-base concepts. Responses were obtained from 260 Form 5 (Grade 11) students from five schools to initially…

Evaluation of the Cross-reactivity of Antidrug Antibodies to CT-P13 and Infliximab Reference Product (Remicade): An Analysis Using Immunoassays Tagged with Both Agents.

PubMed

Reinisch, Walter; Jahnsen, Jørgen; Schreiber, Stefan; Danese, Silvio; Panés, Julián; Balsa, Alejandro; Park, Won; Kim, JiSoo; Lee, Jee Un; Yoo, Dae Hyun

2017-06-01

During two pivotal clinical trials of the infliximab biosimilar CT-P13 (PLANETAS and PLANETRA), antidrug antibodies (ADAs) and neutralising antibodies (NAbs) were detected in the sera of patients treated with CT-P13 and the reference product (RP; Remicade). The aim was to assess the comparability of Remicade- and CT-P13-tagged immunoassays for the detection of ADAs and NAbs using data from these trials, in order to determine the cross-reactivity of CT-P13 and RP ADAs. Sera from patients with rheumatoid arthritis and ankylosing spondylitis were analysed using an electrochemiluminescence (ECL) bridging assay or Gyros immunoassay, tagged with Remicade or CT-P13 at screening, weeks 14, 30 and 54, and the end of study visit. NAb titre was compared at screening and weeks 14 and 30. The proportion of cross-reactive samples was determined and an inter-rater agreement analysis performed to assess the concordance of results between assays. In PLANETAS, 93.1% (94/101) of RP ADA-positive samples and 93.0% (93/100) of RP NAb-positive samples cross-reacted with CT-P13; 99.0% (103/104) of CT-P13 ADA-positive and 98.0% (98/100) of CT-P13 NAb-positive samples cross-reacted with the RP. In PLANETRA, 94.7% (426/450) of RP ADA-positive samples and 94.3% (415/440) of RP NAb-positive samples cross-reacted with CT-P13, and 96.6% (458/474) of CT-P13 ADA-positive and 96.4% (452/469) of CT-P13 NAb-positive samples cross-reacted with the RP. In both studies, there was strong agreement in outcome between assays at all post-screening time points (PLANETAS: Cohen's κ 0.89-0.98 for ADA, 0.86-0.98 for NAb; PLANETRA: 0.92-0.94 for both ADA and NAb, all p < 0.001). Significant concordance between assays was observed for NAb titre at weeks 14 and 30 (PLANETAS: Spearman's ρ 0.73 and 0.74, respectively; PLANETRA: 0.61 and 0.72, respectively; all p < 0.001). This study has demonstrated that ADAs and NAbs against CT-P13 and RP are cross-reactive, indicating that CT-P13 and RP share immunodominant

Acid-base and hormonal abnormalities in dogs with naturally occurring diabetes mellitus.

PubMed

Durocher, Lawren L; Hinchcliff, Kenneth W; DiBartola, Stephen P; Johnson, Susan E

2008-05-01

To examine acid-base and hormonal abnormalities in dogs with diabetes mellitus. Cross-sectional study. 48 dogs with diabetes mellitus and 17 healthy dogs. Blood was collected and serum ketone, glucose, lactate, electrolytes, insulin, glucagon, cortisol, epinephrine, norepinephrine, nonesterified fatty acid, and triglyceride concentrations were measured. Indicators of acid-base status were calculated and compared between groups. Serum ketone and glucose concentrations were significantly higher in diabetic than in healthy dogs, but there was no difference in venous blood pH or base excess between groups. Anion gap and strong ion difference were significantly higher and strong ion gap and serum bicarbonate concentration were significantly lower in the diabetic dogs. There were significant linear relationships between measures of acid-base status and serum ketone concentration, but not between measures of acid-base status and serum lactate concentration. Serum insulin concentration did not differ significantly between groups, but diabetic dogs had a wider range of values. All diabetic dogs with a serum ketone concentration > 1,000 micromol/L had a serum insulin concentration < 5 microU/mL. There were strong relationships between serum ketone concentration and serum glucagon-insulin ratio, serum cortisol concentration, and plasma norepinephrine concentration. Serum beta-hydroxybutyrate concentration, expressed as a percentage of serum ketone concentration, decreased as serum ketone concentration increased. Results suggested that ketosis in diabetic dogs was related to the glucagon-insulin ratio with only low concentrations of insulin required to prevent ketosis. Acidosis in ketotic dogs was attributable largely to high serum ketone concentrations.

Feature-based classification of amino acid substitutions outside conserved functional protein domains.

PubMed

Gemovic, Branislava; Perovic, Vladimir; Glisic, Sanja; Veljkovic, Nevena

2013-01-01

There are more than 500 amino acid substitutions in each human genome, and bioinformatics tools irreplaceably contribute to determination of their functional effects. We have developed feature-based algorithm for the detection of mutations outside conserved functional domains (CFDs) and compared its classification efficacy with the most commonly used phylogeny-based tools, PolyPhen-2 and SIFT. The new algorithm is based on the informational spectrum method (ISM), a feature-based technique, and statistical analysis. Our dataset contained neutral polymorphisms and mutations associated with myeloid malignancies from epigenetic regulators ASXL1, DNMT3A, EZH2, and TET2. PolyPhen-2 and SIFT had significantly lower accuracies in predicting the effects of amino acid substitutions outside CFDs than expected, with especially low sensitivity. On the other hand, only ISM algorithm showed statistically significant classification of these sequences. It outperformed PolyPhen-2 and SIFT by 15% and 13%, respectively. These results suggest that feature-based methods, like ISM, are more suitable for the classification of amino acid substitutions outside CFDs than phylogeny-based tools.

Nucleic acid-based diagnostics for infectious diseases in public health affairs.

PubMed

Yu, Albert Cheung-Hoi; Vatcher, Greg; Yue, Xin; Dong, Yan; Li, Mao Hua; Tam, Patrick H K; Tsang, Parker Y L; Wong, April K Y; Hui, Michael H K; Yang, Bin; Tang, Hao; Lau, Lok-Ting

2012-06-01

Infectious diseases, mostly caused by bacteria and viruses but also a result of fungal and parasitic infection, have been one of the most important public health concerns throughout human history. The first step in combating these pathogens is to get a timely and accurate diagnosis at an affordable cost. Many kinds of diagnostics have been developed, such as pathogen culture, biochemical tests and serological tests, to help detect and fight against the causative agents of diseases. However, these diagnostic tests are generally unsatisfactory because they are not particularly sensitive and specific and are unable to deliver speedy results. Nucleic acid-based diagnostics, detecting pathogens through the identification of their genomic sequences, have shown promise to overcome the above limitations and become more widely adopted in clinical tests. Here we review some of the most popular nucleic acid-based diagnostics and focus on their adaptability and applicability to routine clinical usage. We also compare and contrast the characteristics of different types of nucleic acid-based diagnostics.

The μ3 model of acids and bases: extending the Lewis theory to intermetallics.

PubMed

Stacey, Timothy E; Fredrickson, Daniel C

2012-04-02

A central challenge in the design of new metallic materials is the elucidation of the chemical factors underlying the structures of intermetallic compounds. Analogies to molecular bonding phenomena, such as the Zintl concept, have proven very productive in approaching this goal. In this Article, we extend a foundational concept of molecular chemistry to intermetallics: the Lewis theory of acids and bases. The connection is developed through the method of moments, as applied to DFT-calibrated Hückel calculations. We begin by illustrating that the third and fourth moments (μ(3) and μ(4)) of the electronic density of states (DOS) distribution tune the properties of a pseudogap. μ(3) controls the balance of states above and below the DOS minimum, with μ(4) then determining the minimum's depth. In this way, μ(3) predicts an ideal occupancy for the DOS distribution. The μ(3)-ideal electron count is used to forge a link between the reactivity of transition metals toward intermetallic phase formation, and that of Lewis acids and bases toward adduct formation. This is accomplished through a moments-based definition of acidity which classifies systems that are electron-poor relative to the μ(3)-ideal as μ(3)-acidic, and those that are electron-rich as μ(3)-basic. The reaction of μ(3) acids and bases, whether in the formation of a Lewis acid/base adduct or an intermetallic phase, tends to neutralize the μ(3) acidity or basicity of the reactants. This μ(3)-neutralization is traced to the influence of electronegativity differences at heteroatomic contacts on the projected DOS curves of the atoms involved. The role of μ(3)-acid/base interactions in intermetallic phases is demonstrated through the examination of 23 binary phases forming between 3d metals, the stability range of the CsCl type, and structural trends within the Ti-Ni system.

Acidic-basic properties of three alanine-based peptides containing acidic and basic side chains: comparison between theory and experiment.

PubMed

Makowska, Joanna; Bagińska, Katarzyna; Liwo, Adam; Chmurzyński, Lech; Scheraga, Harold A

2008-01-01

The purpose of this work was to evaluate the effect of the nature of the ionizable end groups, and the solvent, on their acid-base properties in alanine-based peptides. Hence, the acid-base properties of three alanine-based peptides: Ac-KK-(A)(7)-KK-NH(2) (KAK), Ac-OO-(A)(7)-DD-NH(2) (OAD), Ac-KK-(A)(7)-EE-NH(2) (KAE), where A, D, E, K, and O denote alanine, aspartic acid, glutamic acid, lysine, and ornithine, respectively, were determined in water and in methanol by potentiometry. With the availability of these data, the ability of two theoretical methods to simulate pH-metric titration of those peptides was assessed: (i) the electrostatically driven Monte Carlo method with the ECEPP/3 force field and the Poisson-Boltzmann approach to compute solvation energy (EDMC/PB/pH), and (ii) the molecular dynamics method with the AMBER force field and the Generalized Born model (MD/GB/pH). For OAD and KAE, pK(a1) and pK(a2) correspond to the acidic side chains. For all three compounds in both solvents, the pK(a1) value is remarkably lower than the pK(a) of a compound modeling the respective isolated side chain, which can be explained by the influence of the electrostatic field from positively charged ornithine or lysine side chains. The experimental titration curves are reproduced well by the MD/GB/pH approach, the agreement being better if restraints derived from NMR measurements are incorporated in the conformational search. Poorer agreement is achieved by the EDMC/PB/pH method.

Liquid crystal based biosensors for bile acid detection

NASA Astrophysics Data System (ADS)

He, Sihui; Liang, Wenlang; Tanner, Colleen; Fang, Jiyu; Wu, Shin-Tson

2013-03-01

The concentration level of bile acids is a useful indicator for early diagnosis of liver diseases. The prevalent measurement method in detecting bile acids is the chromatography coupled with mass spectrometry, which is precise yet expensive. Here we present a biosensor platform based on liquid crystal (LC) films for the detection of cholic acid (CA). This platform has the advantage of low cost, label-free, solution phase detection and simple analysis. In this platform, LC film of 4-Cyano-4'-pentylbiphenyl (5CB) was hosted by a copper grid supported with a polyimide-coated glass substrate. By immersing into sodium dodecyl sulfate (SDS) solution, the LC film was coated with SDS which induced a homeotropic anchoring of 5CB. Addition of CA introduced competitive adsorption between CA and SDS at the interface, triggering a transition from homeotropic to homogeneous anchoring. The detection limit can be tuned by changing the pH value of the solution from 12uM to 170uM.

History of blood gas analysis. II. pH and acid-base balance measurements.

PubMed

Severinghaus, J W; Astrup, P B

1985-10-01

Electrometric measurement of the hydrogen ion concentration was discovered by Wilhelm Ostwald in Leipzig about 1890 and described thermodynamically by his student Walther Nernst, using the van't Hoff concept of osmotic pressure as a kind of gas pressure, and the Arrhenius concept of ionization of acids, both of which had been formalized in 1887. Hasselbalch, after adapting the pH nomenclature of Sørensen to the carbonic-acid mass equation of Henderson, made the first actual blood pH measurements (with a hydrogen electrode) and proposed that metabolic acid-base imbalance be quantified as the "reduced" pH of blood after equilibration to a carbon dioxide tension (PCO2) of 40 mm Hg. This good idea, coming 40 years before simple blood pH measurements at 37 degrees C became widely available, was never adopted. Instead, Van Slyke developed a concept of acid-base chemistry that depended on measuring plasma CO2 content with his manometric apparatus, a standard method until the 1960s, when it was displaced by the three-electrode method of blood gas analysis. The 1952 polio epidemic in Copenhagen stimulated Astrup to develop a glass electrode in which pH could be measured in blood at 37 degrees C before and after equilibration with known PCO2. He introduced the interpolative measurement of PCO2 and bicarbonate level (later base excess) using only pH measurements and, with Siggaard-Andersen, developed clinical acid-base chemistry. Controversy arose when blood base excess was noted to be altered by acute changes in PCO2 and when abnormalities of base excess were called metabolic acidosis or alkalosis, even when they represented compensation for respiratory abnormalities in PCO2. In the 1970s it became clear that "in-vivo" or "extracellular fluid" base excess (measured at an average extracellular fluid hemoglobin concentration of 5 g) eliminated the error caused by acute changes in PCO2. Base excess is now almost universally used as the index of nonrespiratory acid-base

Natively glycosylated HIV-1 Env structure reveals new mode for antibody recognition of the CD4-binding site

PubMed Central

West, Anthony P; Schamber, Michael; Gazumyan, Anna; Golijanin, Jovana; Seaman, Michael S; Fätkenheuer, Gerd; Klein, Florian; Nussenzweig, Michel C; Bjorkman, Pamela J

2016-01-01

HIV-1 vaccine design is informed by structural studies elucidating mechanisms by which broadly neutralizing antibodies (bNAbs) recognize and/or accommodate N-glycans on the trimeric envelope glycoprotein (Env). Variability in high-mannose and complex-type Env glycoforms leads to heterogeneity that usually precludes visualization of the native glycan shield. We present 3.5-Å- and 3.9-Å-resolution crystal structures of the HIV-1 Env trimer with fully processed and native glycosylation, revealing a glycan shield of high-mannose and complex-type N-glycans, which we used to define complete epitopes of two bNAbs. Env trimer was complexed with 10-1074 (against the V3-loop) and IOMA, a new CD4-binding site (CD4bs) antibody. Although IOMA derives from VH1-2*02, the germline gene of CD4bs-targeting VRC01-class bNAbs, its light chain lacks the short CDRL3 that defines VRC01-class bNAbs. Thus IOMA resembles 8ANC131-class/VH1-46–derived CD4bs bNAbs, which have normal-length CDRL3s. The existence of bNAbs that combine features of VRC01-class and 8ANC131-class antibodies has implications for immunization strategies targeting VRC01-like bNAbs. PMID:27617431

Real-time detection of deoxyribonucleic acid bases via their negative differential conductance signature.

PubMed

Dragoman, D; Dragoman, M

2009-08-01

In this Brief Report, we present a method for the real-time detection of the bases of the deoxyribonucleic acid using their signatures in negative differential conductance measurements. The present methods of electronic detection of deoxyribonucleic acid bases are based on a statistical analysis because the electrical currents of the four bases are weak and do not differ significantly from one base to another. In contrast, we analyze a device that combines the accumulated knowledge in nanopore and scanning tunneling detection and which is able to provide very distinctive electronic signatures for the four bases.

Surface Lewis acid-base properties of polymers measured by inverse gas chromatography.

PubMed

Shi, Baoli; Zhang, Qianru; Jia, Lina; Liu, Yang; Li, Bin

2007-05-18

Surface Lewis acid-base properties are significant for polymers materials. The acid constant, K(a) and base constant, K(b) of many polymers were characterized by some researchers with inverse gas chromatography (IGC) in recent years. In this paper, the surface acid-base constants, K(a) and K(b) of 20 kinds of polymers measured by IGC in recent years are summarized and discussed, including seven polymers characterized in this work. After plotting K(b) versus K(a), it is found that the polymers can be encircled by a triangle. They scatter in two regions of the triangle. Four polymers exist in region I. K(b)/K(a) of the polymers in region I are 1.4-2.1. The other polymers exist in region II. Most of the polymers are relative basic materials.

Acid-base equilibrium dynamics in methanol and dimethyl sulfoxide probed by two-dimensional infrared spectroscopy.

PubMed

Lee, Chiho; Son, Hyewon; Park, Sungnam

2015-07-21

Two-dimensional infrared (2DIR) spectroscopy, which has been proven to be an excellent experimental method for studying thermally-driven chemical processes, was successfully used to investigate the acid dissociation equilibrium of HN3 in methanol (CH3OH) and dimethyl sulfoxide (DMSO) for the first time. Our 2DIR experimental results indicate that the acid-base equilibrium occurs on picosecond timescales in CH3OH but that it occurs on much longer timescales in DMSO. Our results imply that the different timescales of the acid-base equilibrium originate from different proton transfer mechanisms between the acidic (HN3) and basic (N3(-)) species in CH3OH and DMSO. In CH3OH, the acid-base equilibrium is assisted by the surrounding CH3OH molecules which can directly donate H(+) to N3(-) and accept H(+) from HN3 and the proton migrates through the hydrogen-bonded chain of CH3OH. On the other hand, the acid-base equilibrium in DMSO occurs through the mutual diffusion of HN3 and N3(-) or direct proton transfer. Our 2DIR experimental results corroborate different proton transfer mechanisms in the acid-base equilibrium in protic (CH3OH) and aprotic (DMSO) solvents.

Evaluation of the number of ionogenic groups of inulinase by acid-base titration.

PubMed

Kovaleva, T A; Holyavka, M G; Rezvan, S G; Kozhedub, S V

2008-06-01

Acid base titration showed that Aspergillus awamori inulinase includes 178 asparaginic and glutamic acid residues, 20 histidine, 10 serine, and 34 lysine and tyrosine residues. Denaturation temperature for this enzyme was calculated using analysis of the proportion of stabilizing and destabilizing amino acids in the molecule.

Recent advances in understanding trans-epithelial acid-base regulation and excretion mechanisms in cephalopods

PubMed Central

Hu, Marian Y; Hwang, Pung-Pung; Tseng, Yung-Che

2015-01-01

Cephalopods have evolved complex sensory systems and an active lifestyle to compete with fish for similar resources in the marine environment. Their highly active lifestyle and their extensive protein metabolism has led to substantial acid-base regulatory abilities enabling these organisms to cope with CO2 induced acid-base disturbances. In convergence to teleost, cephalopods possess an ontogeny-dependent shift in ion-regulatory epithelia with epidermal ionocytes being the major site of embryonic acid-base regulation and ammonia excretion, while gill epithelia take these functions in adults. Although the basic morphology and excretory function of gill epithelia in cephalopods were outlined almost half a century ago, modern immunohistological and molecular techniques are bringing new insights to the mechanistic basis of acid-base regulation and excretion of nitrogenous waste products (e.g. NH3/NH4+) across ion regulatory epithelia of cephalopods. Using cephalopods as an invertebrate model, recent findings reveal partly conserved mechanisms but also novel aspects of acid-base regulation and nitrogen excretion in these exclusively marine animals. Comparative studies using a range of marine invertebrates will create a novel and exciting research direction addressing the evolution of pH regulatory and excretory systems. PMID:26716070

Improvement of the boron neutron capture therapy (BNCT) by the previous administration of the histone deacetylase inhibitor sodium butyrate for the treatment of thyroid carcinoma.

PubMed

Perona, M; Rodríguez, C; Carpano, M; Thomasz, L; Nievas, S; Olivera, M; Thorp, S; Curotto, P; Pozzi, E; Kahl, S; Pisarev, M; Juvenal, G; Dagrosa, A

2013-08-01

We have shown that boron neutron capture therapy (BNCT) could be an alternative for the treatment of poorly differentiated thyroid carcinoma (PDTC). Histone deacetylase inhibitors (HDACI) like sodium butyrate (NaB) cause hyperacetylation of histone proteins and show capacity to increase the gamma irradiation effect. The purpose of these studies was to investigate the use of the NaB as a radiosensitizer of the BNCT for PDTC. Follicular thyroid carcinoma cells (WRO) and rat thyroid epithelial cells (FRTL-5) were incubated with 1 mM NaB and then treated with boronophenylalanine ¹⁰BPA (10 μg ¹⁰B ml⁻¹) + neutrons, or with 2, 4-bis (α,β-dihydroxyethyl)-deutero-porphyrin IX ¹⁰BOPP (10 μg ¹⁰B ml⁻¹) + neutrons, or with a neutron beam alone. The cells were irradiated in the thermal column facility of the RA-3 reactor (flux = (1.0 ± 0.1) × 10¹⁰ n cm⁻² s⁻¹). Cell survival decreased as a function of the physical absorbed dose in both cell lines. Moreover, the addition of NaB decreased cell survival (p < 0.05) in WRO cells incubated with both boron compounds. NaB increased the percentage of necrotic and apoptotic cells in both BNCT groups (p < 0.05). An accumulation of cells in G2/M phase at 24 h was observed for all the irradiated groups and the addition of NaB increased this percentage. Biodistribution studies of BPA (350 mg kg⁻¹ body weight) 24 h after NaB injection were performed. The in vivo studies showed that NaB treatment increases the amount of boron in the tumor at 2-h post-BPA injection (p < 0.01). We conclude that NaB could be used as a radiosensitizer for the treatment of thyroid carcinoma by BNCT.

HIV-1 maternal and infant variants show similar sensitivity to broadly neutralizing antibodies, but sensitivity varies by subtype

PubMed Central

Jennifer, Mabuka; Leslie, Goo; Maxwel, Majiwa O.; Ruth, Nduati; Julie, Overbaugh

2014-01-01

Rationale To protect against HIV infection, passively transferred and/or vaccine elicited neutralizing antibodies (NAbs) need to effectively target diverse subtypes that are transmitted globally. These variants are a limited subset of those present during chronic infection and display some unique features. In the case of mother-to-child transmission (MTCT), transmitted variants tend to be resistant to neutralization by maternal autologous NAbs. Method To investigate whether variants transmitted during MTCT are generally resistant to HIV-1 specific NAbs, 107 maternal or infant variants representing the dominant HIV-1 subtypes were tested against six recently identified HIV-1-specific broadly neutralizing monoclonal antibodies (bNAbs), NIH45-46W, VRC01, PGT128, PGT121, PG9, and PGT145. Results Infant and maternal variants did not differ in their neutralization sensitivity to individual bNAbs, nor did viruses from transmitting versus non-transmitting mothers, although there was a trend for viruses from transmitting mothers to be less sensitive overall. No single bNAb neutralized all viruses, but a combination of bNAbs that target distinct epitopes covered 100% of the variants tested. Compared to heterosexually transmitted variants, vertically transmitted variants, were significantly more sensitive to neutralization by PGT128 and PGT121 (p=0.03 in both cases) but there were no differences for the other bNAbs. Overall, subtype A variants were significantly more sensitive to NIH45-46 (p=0.04), VRC01 (p=0.002) and PGT145 (p=0.03) compared to the non-subtype A and less sensitive to PGT121 than subtype Cs (p=0.0001). Conclusion A combination of bNAbs against distinct epitopes may be needed to provide maximum coverage against viruses in different modes of transmission and diverse subtypes. PMID:23856624

Effect of low levels of aflatoxin B₁ on performance, biochemical parameters, and aflatoxin B₁ in broiler liver tissues in the presence of monensin and sodium bentonite.

PubMed

Magnoli, A P; Monge, M P; Miazzo, R D; Cavaglieri, L R; Magnoli, C E; Merkis, C I; Cristofolini, A L; Dalcero, A M; Chiacchiera, S M

2011-01-01

Aflatoxins (AF) are a major problem in broiler production and are significant economic and public health burdens worldwide. A commercial sodium bentonite (Na-B) adsorbent was used to prevent the effect of AF [50 µg of aflatoxin B₁ (AFB₁)/kg of feed] in broiler productivity, biochemical parameters, macroscopic and microscopic liver changes, and AFB₁ liver residues. The influence of Na-B (0.3%) and monensin (MON, 100 mg/kg), alone or in combination, was investigated in depth. The dietary treatments were as follows: treatment (T) 1: basal diet (B); T2: B + MON; T3: B + Na-B; T4: B + Na-B + MON; T5: B + AFB₁; T6: B + AFB₁ + Na-B + MON; T7: B + AFB₁ + MON; T8: B + AFB₁ + Na-B. Birds were fed dietary treatments for 28 d (d 18 to 46). No significant differences (P < 0.05) were observed among treatments with respect to broiler performance, biochemical parameters, or relative liver weights. With the exception of T8, all livers showed histopathological alterations, with accumulation of fat vacuoles. The normal appearance of livers from T8 showed the protective effect of Na-B against aflatoxicosis. The residual AFB₁ levels in livers from T5 to T8 ranged from 0.2 to 1.0 ng/g and were higher in livers from T6 (P < 0.05). Results of this study indicate a competition between AFB₁ and MON for adsorption sites on Na-B when feed contains low levels of the toxin, indicating a nonselective adsorption capacity of this particular Na-B. In addition, significant levels of AFB₁ in livers indicate that this determination is an important technique not only for diagnosis of aflatoxicosis in broilers, but also for quality control of avian products.

Design of cinnamaldehyde amino acid Schiff base compounds based on the quantitative structure-activity relationship.

PubMed

Wang, Hui; Jiang, Mingyue; Li, Shujun; Hse, Chung-Yun; Jin, Chunde; Sun, Fangli; Li, Zhuo

2017-09-01

Cinnamaldehyde amino acid Schiff base (CAAS) is a new class of safe, bioactive compounds which could be developed as potential antifungal agents for fungal infections. To design new cinnamaldehyde amino acid Schiff base compounds with high bioactivity, the quantitative structure-activity relationships (QSARs) for CAAS compounds against Aspergillus niger ( A. niger ) and Penicillium citrinum (P. citrinum) were analysed. The QSAR models ( R 2  = 0.9346 for A. niger , R 2  = 0.9590 for P. citrinum, ) were constructed and validated. The models indicated that the molecular polarity and the Max atomic orbital electronic population had a significant effect on antifungal activity. Based on the best QSAR models, two new compounds were designed and synthesized. Antifungal activity tests proved that both of them have great bioactivity against the selected fungi.

Design of cinnamaldehyde amino acid Schiff base compounds based on the quantitative structure–activity relationship

PubMed Central

Wang, Hui; Jiang, Mingyue; Hse, Chung-Yun; Jin, Chunde; Sun, Fangli; Li, Zhuo

2017-01-01

Cinnamaldehyde amino acid Schiff base (CAAS) is a new class of safe, bioactive compounds which could be developed as potential antifungal agents for fungal infections. To design new cinnamaldehyde amino acid Schiff base compounds with high bioactivity, the quantitative structure–activity relationships (QSARs) for CAAS compounds against Aspergillus niger (A. niger) and Penicillium citrinum (P. citrinum) were analysed. The QSAR models (R2 = 0.9346 for A. niger, R2 = 0.9590 for P. citrinum,) were constructed and validated. The models indicated that the molecular polarity and the Max atomic orbital electronic population had a significant effect on antifungal activity. Based on the best QSAR models, two new compounds were designed and synthesized. Antifungal activity tests proved that both of them have great bioactivity against the selected fungi. PMID:28989758

Biocompatibility of a bicarbonate-buffered amino-acid-based solution for peritoneal dialysis.

PubMed

Bender, Thorsten O; Witowski, Janusz; Aufricht, Christoph; Endemann, Michaela; Frei, Ulrich; Passlick-Deetjen, Jutta; Jörres, Achim

2008-09-01

Amino-acid-based peritoneal dialysis (PD) fluids have been developed to improve the nutritional status of PD patients. As they may potentially exacerbate acidosis, an amino-acid-containing solution buffered with bicarbonate (Aminobic) has been proposed to effectively maintain acid-base balance. The aim of this study was to evaluate the mesothelial biocompatibility profile of this solution in comparison with a conventional low-glucose-based fluid. Omentum-derived human peritoneal mesothelial cells (HPMC) were preexposed to test PD solutions for up to 120 min, then allowed to recover in control medium for 24 h, and assessed for heat-shock response, viability, and basal and stimulated cytokine [interleukin (IL)-6] and prostaglandin (PGE(2)) release. Acute exposure of HPMC to conventional low-glucose-based PD solution resulted in a time-dependent increase in heat-shock protein (HSP-72) expression, impaired viability, and reduced ability to release IL-6 in response to stimulation. In contrast, in cells treated with Aminobic, the expression of HSP-72 was significantly lower, and viability and cytokine-producing capacity were preserved and did not differ from those seen in control cells. In addition, exposure to Aminobic increased basal release of IL-6 and PGE(2). These data point to a favorable biocompatibility profile of the amino-acid-based bicarbonate-buffered PD solution toward HPMC.

A stimuli-responsive fluorescence platform for simultaneous determination of D-isoascorbic acid and Tartaric acid based on Maillard reaction product

NASA Astrophysics Data System (ADS)

Zhao, Yanmei; Yuan, Haiyan; Zhang, Xinling; Yang, Jidong

2018-05-01

An activatable fluorescence monitoring platform based on a novel Maillard reaction product from D-glucose and L-arginine was prepared through a facile one-pot approach and applied for simultaneous detection of D-isoascorbic acid and tartaric acid. In this work, the new Maillard reaction product GLA was first obtained, and its fluorescence intensity can be effectively quenched by KMnO4, resulting from a new complex (GLA-KMnO4) formation between GLA and KMnO4. Upon addition of D-isoascorbic acid or tartaric acid, an enhanced fluorescence was observed under the optimumed experimental conditions, indicating a stimuli-responsive fluorescence turn on platform for D-isoascorbic acid or tartaric acid can be developed. The corresponding experimental results showed that this turn on fluorescence sensing platform has a high sensitivity for D-isoascorbic acid or tartaric acid, because the detection limits were 5.9 μM and 21.5 μM, respectively. Additionally, this proposed sensing platform was applied to simultaneously detection of D-isoascorbic acid and tartaric acid in real tap water samples with satisfactory results.

Electrodeposited Fe-Co films prepared from a citric-acid-based plating bath

NASA Astrophysics Data System (ADS)

Yanai, T.; Uto, H.; Shimokawa, T.; Nakano, M.; Fukunaga, H.; Suzuki, K.

2013-06-01

Electrodeposited Fe-Co films are commonly prepared in a boric-acid-based bath. In this research, we applied citric acid instead of boric acid for the plating of Fe-Co films because boron in the waste bath is restricted by environmental-protection regulations in Japan. We evaluated the effect of citric acid on the magnetic and structural properties of the films. The saturation magnetization of the Fe-Co films slightly increased while the Fe content in the Fe-Co films decreased with increasing citric acid concentration. The lowest coercivity value of 240 A/m was obtained at a citric acid concentration of 100 g/L. The plating bath with this citric acid concentration enabled us to obtain Fe-Co films with high saturation magnetizations and smooth surface morphologies.

Bispecific Anti-HIV-1 Antibodies with Enhanced Breadth and Potency.

PubMed

Bournazos, Stylianos; Gazumyan, Anna; Seaman, Michael S; Nussenzweig, Michel C; Ravetch, Jeffrey V

2016-06-16

Broadly neutralizing antibodies (bNAbs) against the HIV-1 envelope glycoprotein (Env) suppress viremia in animal models of HIV-1 and humans. To achieve potent activity without the emergence of viral escape mutants, co-administration of different bNAbs is necessary to target distinct epitopes essential for viral fitness. Here, we report the development of bispecific anti-Env neutralizing antibodies (biNAbs) with potent activity. Synergistic activity of biNAbs was achieved by combining an engineered hinge domain of IgG3 to increase Fab domain flexibility necessary for hetero-bivalent binding to the Env trimer while retaining the functional properties of the IgG1-Fc. Compared to unmodified biNAbs, hinge domain variants exhibited substantially improved neutralization activity, with particular combinations showing evidence of synergistic neutralization potency in vitro and enhanced in vivo therapeutic activity in HIV-1-infected humanized mice. These findings suggest innovative strategies for generating biNAbs with enhanced neutralization breadth and potency, representing ideal candidate molecules for the control of HIV-1 infection. Copyright © 2016 Elsevier Inc. All rights reserved.

Quantitative analyses reveal distinct sensitivities of the capture of HIV-1 primary viruses and pseudoviruses to broadly neutralizing antibodies.

PubMed

Kim, Jiae; Jobe, Ousman; Peachman, Kristina K; Michael, Nelson L; Robb, Merlin L; Rao, Mangala; Rao, Venigalla B

2017-08-01

Development of vaccines capable of eliciting broadly neutralizing antibodies (bNAbs) is a key goal to controlling the global AIDS epidemic. To be effective, bNAbs must block the capture of HIV-1 to prevent viral acquisition and establishment of reservoirs. However, the role of bNAbs, particularly during initial exposure of primary viruses to host cells, has not been fully examined. Using a sensitive, quantitative, and high-throughput qRT-PCR assay, we found that primary viruses were captured by host cells and converted into a trypsin-resistant form in less than five minutes. We discovered, unexpectedly, that bNAbs did not block primary virus capture, although they inhibited the capture of pseudoviruses/IMCs and production of progeny viruses at 48h. Further, viruses escaped bNAb inhibition unless the bNAbs were present in the initial minutes of exposure of virus to host cells. These findings will have important implications for HIV-1 vaccine design and determination of vaccine efficacy. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

pKa cycling of the general acid/base in glycoside hydrolase families 33 and 34.

PubMed

Yu, Haibo; Griffiths, Thomas M

2014-03-28

Glycoside hydrolase families 33 and 34 catalyse the hydrolysis of terminal sialic acid residues from sialyl oligosaccharides and glycoconjugates with a net retention of the stereochemistry at the anomeric centre. It is generally believed that the conserved aspartic acid in the active site functions as a general acid to protonate the hydroxyl group of the departing aglycone during glycosylation, and then as a general base to facilitate the nucleophilic attack of the water molecule on the intermediate state during the deglycosylation reaction. The dual role of the general acid/base places specific demands upon its protonation state, and thus pKa values. However, it is not fully understood how this catalytic residue can achieve such pKa cycling during catalysis. We present both MM and combined QM/MM simulations to characterise the pKa values of the proposed catalytic general acid/base in the glycoside hydrolase families 33 and 34. Collectively, our study suggests that the binding of anionic substrates and the local solvation properties along with the neutralisation of the nearby glutamic acid upon glycosylation modulate the electrostatic environment around the general acid/base to achieve its proper protonation states.

Statistical potential-based amino acid similarity matrices for aligning distantly related protein sequences.

PubMed

Tan, Yen Hock; Huang, He; Kihara, Daisuke

2006-08-15

Aligning distantly related protein sequences is a long-standing problem in bioinformatics, and a key for successful protein structure prediction. Its importance is increasing recently in the context of structural genomics projects because more and more experimentally solved structures are available as templates for protein structure modeling. Toward this end, recent structure prediction methods employ profile-profile alignments, and various ways of aligning two profiles have been developed. More fundamentally, a better amino acid similarity matrix can improve a profile itself; thereby resulting in more accurate profile-profile alignments. Here we have developed novel amino acid similarity matrices from knowledge-based amino acid contact potentials. Contact potentials are used because the contact propensity to the other amino acids would be one of the most conserved features of each position of a protein structure. The derived amino acid similarity matrices are tested on benchmark alignments at three different levels, namely, the family, the superfamily, and the fold level. Compared to BLOSUM45 and the other existing matrices, the contact potential-based matrices perform comparably in the family level alignments, but clearly outperform in the fold level alignments. The contact potential-based matrices perform even better when suboptimal alignments are considered. Comparing the matrices themselves with each other revealed that the contact potential-based matrices are very different from BLOSUM45 and the other matrices, indicating that they are located in a different basin in the amino acid similarity matrix space.

Spherical Nucleic Acids as Intracellular Agents for Nucleic Acid Based Therapeutics

NASA Astrophysics Data System (ADS)

Hao, Liangliang

Recent functional discoveries on the noncoding sequences of human genome and transcriptome could lead to revolutionary treatment modalities because the noncoding RNAs (ncRNAs) can be applied as therapeutic agents to manipulate disease-causing genes. To date few nucleic acid-based therapeutics have been translated into the clinic due to challenges in the delivery of the oligonucleotide agents in an effective, cell specific, and non-toxic fashion. Unmodified oligonucleotide agents are destroyed rapidly in biological fluids by enzymatic degradation and have difficulty crossing the plasma membrane without the aid of transfection reagents, which often cause inflammatory, cytotoxic, or immunogenic side effects. Spherical nucleic acids (SNAs), nanoparticles consisting of densely organized and highly oriented oligonucleotides, pose one possible solution to circumventing these problems in both the antisense and RNA interference (RNAi) pathways. The unique three dimensional architecture of SNAs protects the bioactive oligonucleotides from unspecific degradation during delivery and supports their targeting of class A scavenger receptors and endocytosis via a lipid-raft-dependent, caveolae-mediated pathway. Owing to their unique structure, SNAs are able to cross cell membranes and regulate target genes expression as a single entity, without triggering the cellular innate immune response. Herein, my thesis has focused on understanding the interactions between SNAs and cellular components and developing SNA-based nanostructures to improve therapeutic capabilities. Specifically, I developed a novel SNA-based, nanoscale agent for delivery of therapeutic oligonucleotides to manipulate microRNAs (miRNAs), the endogenous post-transcriptional gene regulators. I investigated the role of SNAs involving miRNAs in anti-cancer or anti-inflammation responses in cells and in in vivo murine disease models via systemic injection. Furthermore, I explored using different strategies to construct

Acid-Base Interactions of Polystyrene Sulfonic Acid in Amorphous Solid Dispersions Using a Combined UV/FTIR/XPS/ssNMR Study.

PubMed

Song, Yang; Zemlyanov, Dmitry; Chen, Xin; Nie, Haichen; Su, Ziyang; Fang, Ke; Yang, Xinghao; Smith, Daniel; Byrn, Stephen; Lubach, Joseph W

2016-02-01

This study investigates the potential drug-excipient interactions of polystyrene sulfonic acid (PSSA) and two weakly basic anticancer drugs, lapatinib (LB) and gefitinib (GB), in amorphous solid dispersions. Based on the strong acidity of the sulfonic acid functional group, PSSA was hypothesized to exhibit specific intermolecular acid-base interactions with both model basic drugs. Ultraviolet (UV) spectroscopy identified red shifts, which correlated well with the color change observed in lapatinib-PSSA solutions. Fourier transform infrared (FTIR) spectra suggest the protonation of the quinazoline nitrogen atom in both model compounds, which agrees well with data from the crystalline ditosylate salt of lapatinib. X-ray photoelectron spectroscopy (XPS) detected increases in binding energy of the basic nitrogen atoms in both lapatinib and gefitinib, strongly indicating protonation of these nitrogen atoms. (15)N solid-state NMR spectroscopy provided direct spectroscopic evidence for protonation of the quinazoline nitrogen atoms in both LB and GB, as well as the secondary amine nitrogen atom in LB and the tertiary amine nitrogen atom in GB. The observed chemical shifts in the LB-PSSA (15)N spectrum also agree very well with the lapatinib ditosylate salt where proton transfer is known. Additionally, the dissolution and physical stability behaviors of both amorphous solid dispersions were examined. PSSA was found to significantly improve the dissolution of LB and GB and effectively inhibit the crystallization of LB and GB under accelerated storage conditions due to the beneficial strong intermolecular acid-base interaction between the sulfonic acid groups and basic nitrogen centers.

Acid and Base Stress and Transcriptomic Responses in Bacillus subtilis▿†

PubMed Central

Wilks, Jessica C.; Kitko, Ryan D.; Cleeton, Sarah H.; Lee, Grace E.; Ugwu, Chinagozi S.; Jones, Brian D.; BonDurant, Sandra S.; Slonczewski, Joan L.

2009-01-01

Acid and base environmental stress responses were investigated in Bacillus subtilis. B. subtilis AG174 cultures in buffered potassium-modified Luria broth were switched from pH 8.5 to pH 6.0 and recovered growth rapidly, whereas cultures switched from pH 6.0 to pH 8.5 showed a long lag time. Log-phase cultures at pH 6.0 survived 60 to 100% at pH 4.5, whereas cells grown at pH 7.0 survived <15%. Cells grown at pH 9.0 survived 40 to 100% at pH 10, whereas cells grown at pH 7.0 survived <5%. Thus, growth in a moderate acid or base induced adaptation to a more extreme acid or base, respectively. Expression indices from Affymetrix chip hybridization were obtained for 4,095 protein-encoding open reading frames of B. subtilis grown at external pH 6, pH 7, and pH 9. Growth at pH 6 upregulated acetoin production (alsDS), dehydrogenases (adhA, ald, fdhD, and gabD), and decarboxylases (psd and speA). Acid upregulated malate metabolism (maeN), metal export (czcDO and cadA), oxidative stress (catalase katA; OYE family namA), and the SigX extracytoplasmic stress regulon. Growth at pH 9 upregulated arginine catabolism (roc), which generates organic acids, glutamate synthase (gltAB), polyamine acetylation and transport (blt), the K+/H+ antiporter (yhaTU), and cytochrome oxidoreductases (cyd, ctaACE, and qcrC). The SigH, SigL, and SigW regulons were upregulated at high pH. Overall, greater genetic adaptation was seen at pH 9 than at pH 6, which may explain the lag time required for growth shift to high pH. Low external pH favored dehydrogenases and decarboxylases that may consume acids and generate basic amines, whereas high external pH favored catabolism-generating acids. PMID:19114526

Acid-base disturbance in patients with cirrhosis: relation to hemodynamic dysfunction.

PubMed

Henriksen, Jens H; Bendtsen, Flemming; Møller, Søren

2015-08-01

Acid-base disturbances were investigated in patients with cirrhosis in relation to hemodynamic derangement to analyze the hyperventilatory effects and the metabolic compensation. A total of 66 patients with cirrhosis and 44 controls were investigated during a hemodynamic study. Hyperventilatory hypocapnia was present in all patients with cirrhosis and progressed from Child class A to C (P<0.01). Arterial pH increased significantly from class A to C (P<0.001) and was correlated inversely to the mean arterial blood pressure (r=-0.30, P<0.02), systemic vascular resistance (r=-0.25, P<0.05), indocyanine green clearance (r=-0.37, P<0.005), and serum sodium (r=-0.38, P<0.002). Metabolic compensation was shown by a reduced standard base excess in all patients (P<0.001). Standard base excess contained elements related to changes in serum albumin, water dilution, and effects of unidentified ions (all P<0.001). A significant hepatic component in the acid-base disturbances could not be identified. Hypocapnic alkalosis is related to disease severity and hyperdynamic systemic circulation in patients with cirrhosis. The metabolic compensation includes alterations in serum albumin and water retention that may result in a delicate acid-base balance in these patients.

Effect of supersaturation on L-glutamic acid polymorphs under droplet-based microchannels

NASA Astrophysics Data System (ADS)

Jiang, Nan; Wang, Zhanzhong; Dang, Leping; Wei, Hongyuan

2016-07-01

Supersaturation is an important controlling factor for crystallization process and polymorphism. Droplet-based microchannels and conventional crystallization were used to investigate polymorphs of L-gluatamic acid in this work. The results illustrate that it is easy to realize the accurate and rapid control of the crystallization temperature in the droplets, which is especially beneficial to heat and mass transfer during crystallization. It is also noted that higher degree of supersaturation favors the nucleation of α crystal form, while lower degree of supersaturation favors the nucleation of β crystal form under droplet-based microchannels for L-gluatamic acid. In addition, there is a different nucleation behavior to be found under droplet-based microchannels both for the β form and α form of L-glutamic acid. This new finding can provide important insight into the development and design of investigation meanings for drug polymorph.

Surface acid-base properties and hydration/dehydration mechanisms of aluminum (hydr)oxides.

PubMed

Yang, Xiaofang; Sun, Zhongxi; Wang, Dongsheng; Forsling, Willis

2007-04-15

In this paper, surface physiochemical properties of three typical aluminas, gamma-Al(OH)3, gamma-Al2O3, and alpha-Al2O3, were investigated by means of XRD, SEM, TEM, BET surface area, TG/DTA, and potentiometric titration techniques. Based on the titration data, surface protonation and deprotonation constants were determined using the constant capacitance model (CCM). The emphasis of this research was laid on the comparison of the crystal structure, surface hydration/dehydration and acid-base properties of these three typical alumina minerals. The calculation results revealed that the surface acidity of the aluminas is in the order of alpha-Al2O3>gamma-Al(OH)3>gamma-Al2O3 after being hydrated for 1 h. The correlation between the hydration/dehydration mechanisms of alumina and its acid/base properties is discussed.

Seroprevalence of neutralizing antibodies against adenovirus type 14 and 55 in healthy adults in Southern China

PubMed Central

Zheng, Xuehua; Rong, Xia; Feng, Ying; Sun, Xikui; Li, Liang; Wang, Qian; Wang, Min; Liu, Wenkuan; Li, Chufang; Yang, Yiyu; Zhou, Rong; Lu, Jiahai; Feng, Liqiang; Chen, Ling

2017-01-01

Re-emerging human adenovirus types 14 (Ad14) and 55 (Ad55) have caused severe respiratory diseases and even deaths during recent outbreaks. However, the seroprevalence of neutralizing antibodies (nAbs) in healthy adults, which may reflect previous circulation and help to predict potential outbreaks, remains unclear. In this study, we established micro-neutralizing (MN) assays on the basis of recombinant Ad14 and Ad55 reporter viruses, and we investigated serum nAbs in healthy blood donors from Southern China. We found that the overall seropositive rates were 24.8% and 22.4% for Ad14 and Ad55 nAbs, respectively. The seropositive rates were low in individuals younger than 20, and they gradually increased with age. Ad55-seropositive individuals tended to have high nAb titers (>1000), while low (72–200) and moderate (201–1000) nAb levels were frequently observed in Ad14-seropositive ones. Surprisingly, the seropositive rates and nAb levels were associated with the blood type but not the gender of the blood donors, with type AB individuals displaying higher seropositive rates and nAb levels. Interestingly, a significant positive correlation was observed between Ad14 and Ad55 seroprevalence, and higher titers of nAbs were detected in double-positive individuals compared to single-positive ones. These results clarified the human humoral immune responses against Ad14 and Ad55 and revealed a low level of herd immunity in some subpopulations, which emphasized the importance of monitoring these two highly virulent adenoviruses and reinforced the development of prophylactic vaccines. PMID:28588291

Sodium Benzoate, a Food Additive and a Metabolite of Cinnamon, Enriches Regulatory T Cells via STAT6-Mediated Upregulation of TGF-β.

PubMed

Kundu, Madhuchhanda; Mondal, Susanta; Roy, Avik; Martinson, Jeffrey L; Pahan, Kalipada

2016-10-15

Upregulation and/or maintenance of regulatory T cells (Tregs) during autoimmune insults may have therapeutic efficacy in autoimmune diseases. Earlier we have reported that sodium benzoate (NaB), a metabolite of cinnamon and a Food and Drug Administration-approved drug against urea cycle disorders, upregulates Tregs and protects mice from experimental allergic encephalomyelitis, an animal model of multiple sclerosis. However, mechanisms by which NaB increases Tregs are poorly understood. Because TGF-β is an important inducer of Tregs, we examined the effect of NaB on the status of TGF-β. In this study, we demonstrated that NaB induced the expression of TGF-β mRNA and protein in normal as well as proteolipid protein-primed splenocytes. The presence of a consensus STAT6 binding site in the promoter of the TGF-β gene, activation of STAT6 in splenocytes by NaB, recruitment of STAT6 to the TGF-β promoter by NaB, and abrogation of NaB-induced expression of TGF-β in splenocytes by small interfering RNA knockdown of STAT6 suggest that NaB induces the expression of TGF-β via activation of STAT6. Furthermore, we demonstrated that blocking of TGF-β by neutralizing Abs abrogated NaB-mediated protection of Tregs and experimental allergic encephalomyelitis. These studies identify a new function of NaB in upregulating TGF-β via activation of STAT6, which may be beneficial in MS patients. Copyright © 2016 by The American Association of Immunologists, Inc.

Sodium Benzoate, a Metabolite of Cinnamon and a Food Additive, Upregulates Ciliary Neurotrophic Factor in Astrocytes and Oligodendrocytes.

PubMed

Modi, Khushbu K; Jana, Malabendu; Mondal, Susanta; Pahan, Kalipada

2015-11-01

Ciliary neurotrophic factor (CNTF) is a promyelinating trophic factor that plays an important role in multiple sclerosis (MS). However, mechanisms by which CNTF expression could be increased in the brain are poorly understood. Recently we have discovered anti-inflammatory and immunomodulatory activities of sodium benzoate (NaB), a metabolite of cinnamon and a widely-used food additive. Here, we delineate that NaB is also capable of increasing the mRNA and protein expression of CNTF in primary mouse astrocytes and oligodendrocytes and primary human astrocytes. Accordingly, oral administration of NaB and cinnamon led to the upregulation of astroglial and oligodendroglial CNTF in vivo in mouse brain. Induction of experimental allergic encephalomyelitis, an animal model of MS, reduced the level of CNTF in the brain, which was restored by oral administration of cinnamon. While investigating underlying mechanisms, we observed that NaB induced the activation of protein kinase A (PKA) and H-89, an inhibitor of PKA, abrogated NaB-induced expression of CNTF. The activation of cAMP response element binding (CREB) protein by NaB, the recruitment of CREB and CREB-binding protein to the CNTF promoter by NaB and the abrogation of NaB-induced expression of CNTF in astrocytes by siRNA knockdown of CREB suggest that NaB increases the expression of CNTF via the activation of CREB. These results highlight a novel myelinogenic property of NaB and cinnamon, which may be of benefit for MS and other demyelinating disorders.

Acid-base and ion balance in fishes with bimodal respiration.

PubMed

Shartau, R B; Brauner, C J

2014-03-01

The evolution of air breathing during the Devonian provided early fishes with bimodal respiration with a stable O2 supply from air. This was, however, probably associated with challenges and trade-offs in terms of acid-base balance and ionoregulation due to reduced gill:water interaction and changes in gill morphology associated with air breathing. While many aspects of acid-base and ionoregulation in air-breathing fishes are similar to water breathers, the specific cellular and molecular mechanisms involved remain largely unstudied. In general, reduced ionic permeability appears to be an important adaptation in the few bimodal fishes investigated but it is not known if this is a general characteristic. The kidney appears to play an important role in minimizing ion loss to the freshwater environment in the few species investigated, and while ion uptake across the gut is probably important, it has been largely unexplored. In general, air breathing in facultative air-breathing fishes is associated with an acid-base disturbance, resulting in an increased partial pressure of arterial CO2 and a reduction in extracellular pH (pHE ); however, several fishes appear to be capable of tightly regulating tissue intracellular pH (pHI ), despite a large sustained reduction in pHE , a trait termed preferential pHI regulation. Further studies are needed to determine whether preferential pHI regulation is a general trait among bimodal fishes and if this confers reduced sensitivity to acid-base disturbances, including those induced by hypercarbia, exhaustive exercise and hypoxia or anoxia. Additionally, elucidating the cellular and molecular mechanisms may yield insight into whether preferential pHI regulation is a trait ultimately associated with the early evolution of air breathing in vertebrates. © 2014 The Fisheries Society of the British Isles.

β-Amino acid catalyzed asymmetric Michael additions: design of organocatalysts with catalytic acid/base dyad inspired by serine proteases.

PubMed

Yang, Hui; Wong, Ming Wah

2011-09-16

A new type of chiral β-amino acid catalyst has been computationally designed, mimicking the enzyme catalysis of serine proteases. Our catalyst approach is based on the bioinspired catalytic acid/base dyad, namely, a carboxyl and imidazole pair. DFT calculations predict that this designed organocatalyst catalyzes Michael additions of aldehydes to nitroalkenes with excellent enantioselectivities and remarkably high anti diastereoselectivities. The unusual stacked geometry of the enamine intermediate, hydrogen bonding network, and the adoption of an exo transition state are the keys to understand the stereoselectivity. © 2011 American Chemical Society

A Comparative Study of French and Turkish Students' Ideas on Acid-Base Reactions

ERIC Educational Resources Information Center

Cokelez, Aytekin

2010-01-01

The goal of this comparative study was to determine the knowledge that French and Turkish upper secondary-school students (grades 11 and 12) acquire on the concept of acid-base reactions. Following an examination of the relevant curricula and textbooks in the two countries, 528 students answered six written questions about the acid-base concept.…

Microtensile strength of spruce pine after exposure to acids and bases

Treesearch

Floyd G. Manwiller; Paul R. Godfrey

1972-01-01

Earlywood and latewood microtensile specimens from 12 trees of Pinus glabra Wal. were subjected to 10-percent solution of 5 acids and 3 bases at 90oC for up to 3 hours. Hydrochloric and sulfuric acids were the most damaging, lowering maximum tensile strength 27 and 17 percent in earlywood and 36 and 39 percent in latewood; they...

A qualitative study of high school students' pre- and post-instructional conceptions in acid-base chemistry

NASA Astrophysics Data System (ADS)

Sheppard, Keith

This study investigated high school students' understanding of acid-base chemistry, prior to and after formal chemistry instruction. Sixteen students enrolled in a regular chemistry course were interviewed three times during the school year; before and after studying the topic of acids and bases and then while conducting a titration using a microcomputer-based laboratory (MBL). Oral, pictorial and graphical data were collected in a variety of acid-base practical tasks. The data were analyzed in two parts; first, common themes, ideas and alternative conceptions that students held were identified; second, profiles of each students were made to determine changes in their conceptions due to instruction. The findings showed that students had considerable difficulty with several areas of acid-base chemistry and did not develop an integrated conceptual understanding of the topic. Students were unable to describe acid-base concepts accurately and revealed a number of alternative conceptions, which remained unchanged by instruction. Specific areas of difficulty included the concepts of pH, neutralization, strength and the theoretical descriptions of acids and bases. Further, most students could not relate the concepts to actual solutions and were unable to describe acid-base phenomena at a sub-microscopic level. Student difficulties stemmed from a lack of understanding of some underlying and fundamental chemistry, such as the nature of chemical change and the particulate nature of matter. A number of factors were identified as contributing to these difficulties, and included the overstuffed nature of introductory chemistry itself, the emphasis in instruction on solving numerical problems and the dominant role played by the textbook. Further, the conceptual density of acid-base chemistry, the confusing nature of acid-base terminology and the lack of agreement about what material should be included in the chemistry curriculum were viewed as problematic. The study calls for a

HIV-specific Fc effector function early in infection predicts the development of broadly neutralizing antibodies

PubMed Central

Richardson, Simone I.; Mabvakure, Batsirai; Mkhize, Nonhlanhla N.; Moore, Penny L.; Alter, Galit

2018-01-01

While the induction of broadly neutralizing antibodies (bNAbs) is a major goal of HIV vaccination strategies, there is mounting evidence to suggest that antibodies with Fc effector function also contribute to protection against HIV infection. Here we investigated Fc effector functionality of HIV-specific IgG plasma antibodies over 3 years of infection in 23 individuals, 13 of whom developed bNAbs. Antibody-dependent cellular phagocytosis (ADCP), complement deposition (ADCD), cellular cytotoxicity (ADCC) and cellular trogocytosis (ADCT) were detected in almost all individuals with levels of activity increasing over time. At 6 months post-infection, individuals with bNAbs had significantly higher levels of ADCD and ADCT that correlated with antibody binding to C1q and FcγRIIa respectively. In addition, antibodies from individuals with bNAbs showed more IgG subclass diversity to multiple HIV antigens which also correlated with Fc polyfunctionality. Germinal center activity represented by CXCL13 levels and expression of activation-induced cytidine deaminase (AID) was found to be associated with neutralization breadth, Fc polyfunctionality and IgG subclass diversity. Overall, multivariate analysis by random forest classification was able to group bNAb individuals with 85% sensitivity and 80% specificity based on the properties of their antibody Fc early in HIV infection. Thus, the Fc effector function profile predicted the development of neutralization breadth in this cohort, suggesting that intrinsic immune factors within the germinal center provide a mechanistic link between the Fc and Fab of HIV-specific antibodies. PMID:29630668

Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits

PubMed Central

2014-01-01

Background The trimeric envelope glycoproteins (Env) on the surface of HIV-1 virions are the targets for neutralizing antibodies (NAbs). No candidate HIV-1 immunogen has yet induced potent, broadly active NAbs (bNAbs). Part of the explanation may be that previously tested Env proteins inadequately mimic the functional, native Env complex. Trimerization and the proteolytic processing of Env precursors into gp120 and gp41 profoundly alter antigenicity, but soluble cleaved trimers are too unstable to serve as immunogens. By introducing stabilizing mutations (SOSIP), we constructed soluble, cleaved Env trimers derived from the HIV-1 subtype A isolate BG505 that resemble native Env spikes on virions both structurally and antigenically. Results We used surface plasmon resonance (SPR) to quantify antibody binding to different forms of BG505 Env: the proteolytically cleaved SOSIP.664 trimers, cleaved gp120-gp41ECTO protomers, and gp120 monomers. Non-NAbs to the CD4-binding site bound only marginally to the trimers but equally well to gp120-gp41ECTO protomers and gp120 monomers, whereas the bNAb VRC01, directed to the CD4bs, bound to all three forms. In contrast, bNAbs to V1V2 glycan-dependent epitopes bound preferentially (PG9 and PG16) or exclusively (PGT145) to trimers. We also explored the antigenic consequences of three different features of SOSIP.664 gp140 trimers: the engineered inter-subunit disulfide bond, the trimer-stabilizing I559P change in gp41ECTO, and proteolytic cleavage at the gp120-gp41ECTO junction. Each of these three features incrementally promoted native-like trimer antigenicity. We compared Fab and IgG versions of bNAbs and validated a bivalent model of IgG binding. The NAbs showed widely divergent binding kinetics and degrees of binding to native-like BG505 SOSIP.664. High off-rate constants and low stoichiometric estimates of NAb binding were associated with large amounts of residual infectivity after NAb neutralization of the corresponding BG505.T

Competitive/co-operative interactions in acid base sandwich: role of cation vs. substituents.

PubMed

Kalpana, Ayyavoo; Akilandeswari, Lakshminarayanan

2017-11-15

The cation-π interaction can be envisaged as a lewis acid base interaction, and it is in line with Pearson's acid base concept. The critical examination of interactions between the π-acids (alkali metal cations - Li + , Na + and alkaline earth metal cations Mg 2+ , Ca 2+ ) on one face and tripodal Cr(CO) 3 moiety on the other π face of substituted arenes demonstrates the role of cation and substitutents in manipulating the interactions between them. The interaction of the two π acids on both faces of arene is not expectedly additive, rather it shows either depreciation of interaction energy revealing the competition of acids toward the base or enhancement of interaction energy denoting a cooperative effect. Among the metal cations under study, Mg 2+ shows a cooperative gesture. Although the substituents play a meek role, they unfailingly exert their electronic effects and are amply documented by excellent correlation of various parameters with the Hammett constant σ m . The elusive switching of λ max from the UV to IR region on binding Mg 2+ with substituted arene-Cr(CO) 3 complex is a characteristic clue that TDDFT can help design the ionic sensors for Mg 2+ cations.

Hubble Nabs Space Invaders?

NASA Image and Video Library

2017-12-08

The gravitational field surrounding this massive cluster of galaxies, Abell 68, acts as a natural lens in space to brighten and magnify the light coming from very distant background galaxies. Like a fun house mirror, lensing creates a fantasy landscape of arc-like images and mirror images of background galaxies. The foreground cluster is 2 billion light-years away, and the lensed images come from galaxies far behind it. In this photo, the image of a spiral galaxy at upper left has been stretched and mirrored into a shape similar to that of a simulated alien from the classic 1970s computer game "Space Invaders!" A second, less distorted image of the same galaxy appears to the left of the large, bright elliptical galaxy. In the upper right of the photo is another striking feature of the image that is unrelated to gravitational lensing. What appears to be purple liquid dripping from a galaxy is a phenomenon called ram-pressure stripping. The gas clouds within the galaxy are being stripped out and heated up as the galaxy passes through a region of denser intergalactic gas. This image was taken in infrared light by Hubble’s Wide Field Camera 3, and combined with near-infrared observations from Hubble’s Advanced Camera for Surveys. The image is based in part on data spotted by Nick Rose in the Hubble’s Hidden Treasures image processing competition. The Hubble Space Telescope is a project of international cooperation between NASA and the European Space Agency. NASA's Goddard Space Flight Center in Greenbelt, Md., manages the telescope. The Space Telescope Science Institute (STScI) in Baltimore, Md., conducts Hubble science operations. STScI is operated by the Association of Universities for Research in Astronomy, Inc., in Washington. Credit: NASA and ESA Acknowledgement: N. Rose For image files and more information about Abell 68, visit: hubblesite.org/news/2013/09 www.spacetelescope.org/news/heic04 heritage.stsci.edu/2013/09 www

Hubble Nabs Space Invaders?

NASA Image and Video Library

2017-12-08

The gravitational field surrounding this massive cluster of galaxies, Abell 68, acts as a natural lens in space to brighten and magnify the light coming from very distant background galaxies. Like a fun house mirror, lensing creates a fantasy landscape of arc-like images and mirror images of background galaxies. The foreground cluster is 2 billion light-years away, and the lensed images come from galaxies far behind it. In this photo, the image of a spiral galaxy at upper left has been stretched and mirrored into a shape similar to that of a simulated alien from the classic 1970s computer game "Space Invaders!" A second, less distorted image of the same galaxy appears to the left of the large, bright elliptical galaxy. In the upper right of the photo is another striking feature of the image that is unrelated to gravitational lensing. What appears to be purple liquid dripping from a galaxy is a phenomenon called ram-pressure stripping. The gas clouds within the galaxy are being stripped out and heated up as the galaxy passes through a region of denser intergalactic gas. This image was taken in infrared light by Hubble’s Wide Field Camera 3, and combined with near-infrared observations from Hubble’s Advanced Camera for Surveys. The image is based in part on data spotted by Nick Rose in the Hubble’s Hidden Treasures image processing competition. The Hubble Space Telescope is a project of international cooperation between NASA and the European Space Agency. NASA's Goddard Space Flight Center in Greenbelt, Md., manages the telescope. The Space Telescope Science Institute (STScI) in Baltimore, Md., conducts Hubble science operations. STScI is operated by the Association of Universities for Research in Astronomy, Inc., in Washington. To read more go to: 1.usa.gov/Z6uDUp Credit: NASA and ESA Acknowledgement: N. Rose For image files and more information about Abell 68, visit: hubblesite.org/news/2013/09 www.spacetelescope.org/news/heic04 heritage.stsci.edu/2013/09 www

A stimuli-responsive fluorescence platform for simultaneous determination of d-isoascorbic acid and Tartaric acid based on Maillard reaction product.

PubMed

Zhao, Yanmei; Yuan, Haiyan; Zhang, Xinling; Yang, Jidong

2018-05-05

An activatable fluorescence monitoring platform based on a novel Maillard reaction product from d-glucose and L-arginine was prepared through a facile one-pot approach and applied for simultaneous detection of d-isoascorbic acid and tartaric acid. In this work, the new Maillard reaction product GLA was first obtained, and its fluorescence intensity can be effectively quenched by KMnO 4 , resulting from a new complex (GLA-KMnO 4 ) formation between GLA and KMnO 4 . Upon addition of d-isoascorbic acid or tartaric acid, an enhanced fluorescence was observed under the optimumed experimental conditions, indicating a stimuli-responsive fluorescence turn on platform for d-isoascorbic acid or tartaric acid can be developed. The corresponding experimental results showed that this turn on fluorescence sensing platform has a high sensitivity for d-isoascorbic acid or tartaric acid, because the detection limits were 5.9μM and 21.5μM, respectively. Additionally, this proposed sensing platform was applied to simultaneously detection of d-isoascorbic acid and tartaric acid in real tap water samples with satisfactory results. Copyright © 2018 Elsevier B.V. All rights reserved.

Poly(ester amide)s based on (L)-lactic acid oligomers and α-amino acids: influence of the α-amino acid side chain in the poly(ester amide)s properties.

PubMed

Fonseca, Ana C; Coelho, Jorge F J; Valente, Joana F A; Correia, Tiago R; Correia, Ilídio J; Gil, Maria H; Simões, Pedro N

2013-01-01

Novel biodegradable and low cytotoxic poly(ester amide)s (PEAs) based on α-amino acids and (L)-lactic acid (L-LA) oligomers were successfully synthesized by interfacial polymerization. The chemical structure of the new polymers was confirmed by spectroscopic analyses. Further characterization suggests that the α-amino acid plays a critical role on the final properties of the PEA. L-phenylalanine provides PEAs with higher glass transition temperature, whereas glycine enhances the crystallinity. The hydrolytic degradation in PBS (pH = 7.4) at 37 °C also depends on the α-amino acid, being faster for glycine-based PEAs. The cytotoxic profiles using fibroblast human cells indicate that the PEAs did not elicit an acute cytotoxic effect. The strategy presented in this work opens the possibility of synthesizing biodegradable PEAs with low citotoxicity by an easy and fast method. It is worth to mention also that the properties of these materials can be fine-tuned only by changing the α-amino acid.

Milk and acid-base balance: proposed hypothesis versus scientific evidence.

PubMed

Fenton, Tanis R; Lyon, Andrew W

2011-10-01

Recently the lay press has claimed a hypothetical association among dairy product consumption, generation of dietary acid, and harm to human health. This theoretical association is based on the idea that the protein and phosphate in milk and dairy products make them acid-producing foods, which cause our bodies to become acidified, promoting diseases of modern civilization. Some authors have suggested that dairy products are not helpful and perhaps detrimental to bone health because higher osteoporotic fracture incidence is observed in countries with higher dairy product consumption. However, scientific evidence does not support any of these claims. Milk and dairy products neither produce acid upon metabolism nor cause metabolic acidosis, and systemic pH is not influenced by diet. Observations of higher dairy product intake in countries with prevalent osteoporosis do not hold when urban environments are compared, likely due to physical labor in rural locations. Milk and other dairy products continue to be a good source of dietary protein and other nutrients. Key teaching points: Measurement of an acidic pH urine does not reflect metabolic acidosis or an adverse health condition. The modern diet, and dairy product consumption, does not make the body acidic. Alkaline diets alter urine pH but do not change systemic pH. Net acid excretion is not an important influence of calcium metabolism. Milk is not acid producing. Dietary phosphate does not have a negative impact on calcium metabolism, which is contrary to the acid-ash hypothesis.

Redox and Lewis acid-base activities through an electronegativity-hardness landscape diagram.

PubMed

Das, Ranjita; Vigneresse, Jean-Louis; Chattaraj, Pratim Kumar

2013-11-01

Chemistry is the science of bond making and bond breaking which requires redistribution of electron density among the reactant partners. Accordingly acid-base and redox reactions form cardinal components in all branches of chemistry, e.g., inorganic, organic, physical or biochemistry. That is the reason it forms an integral part of the undergraduate curriculum all throughout the globe. In an electronegativity (χ)- hardness (η) landscape diagram the diagonal χ = η line separates reducing agents from oxidizing agents as well as Lewis acids from Lewis bases. While electronegativity is related to the degree of electron transfer between two reactants, hardness is related to the resistance to that process. Accordingly the electronegativities of oxidizing agents/Lewis acids are generally greater than the corresponding hardness values and the reverse is true for reducing agents/Lewis bases. Electrophiles and nucleophiles are also expected to follow similar trends.

Effects of imposed acid-base derangement on the cardiovascular effects and pharmacokinetics of bupivacaine and thiopental.

PubMed

Mather, Laurence E; Ladd, Leigh A; Copeland, Susan E; Chang, Dennis H-T

2004-06-01

By changing physicochemical properties such as effective lipophilicity, changes in blood pH could alter the distribution, elimination, and effects of weakly ionizing drugs. The authors examined the outcome of imposed acid-base derangement on cardiovascular effects and myocardial and whole body pharmacokinetics of bupivacaine, a weak base, and thiopental, a weak acid. Intravenous infusions of rac-bupivacaine HCl (37.5 mg) or rac-thiopental sodium (250 mg, subanesthetic dose) were administered over 3 min to previously instrumented conscious ewes with normal blood pH, acidemia imposed by lactic acid infusion, or alkalemia imposed by bicarbonate infusion. Hemodynamic and electrocardiographic effects were recorded; arterial and coronary sinus drug blood concentrations were analyzed by chiral high-performance liquid chromatography. Bupivacaine decreased myocardial contractility, coronary perfusion, heart rate, and cardiac output; however, cardiac output and stroke volume were not as affected by bupivacaine with acidemia. Thiopental decreased myocardial contractility and stroke volume and increased heart rate; acidemia enhanced the tachycardia and produced a greater decrease in stroke volume than with alkalemia. Taken as a whole, the cardiovascular changes were not systematically modified by acid-base derangement. Overall, the tissue distribution of bupivacaine was favored by alkalemia, but thiopental pharmacokinetics were essentially unaffected by acid-base derangement. Acid-base derangement did not influence the kinetics of either drug enantioselectively. At the doses used, the hemodynamic and electrocardiographic effects of bupivacaine and thiopental were not systematically modified by acid-base derangement, nor were there changes in regional or whole body pharmacokinetics of either drug that were clearly related to acid-base status.

Design of a Program for Expert Diagnosis of Acid Base and Electrolyte Disturbances,

DTIC Science & Technology

1979-05-01

PIP) is a frame based [23) program for taking the present illnrvc irs the doina in of renal diseases. The PIP data base is implemented using disease...I- AD—A 078 ‘+13 MASSACHUSETTS INST OF TECH CAMBRIDGE LAB FOR COMPUTE—ETC F/B 6/5 DESIGN OF A PROGRA M FOR EXPERT DIAGNOSIS OF ACID BASE AND ELECT...132 / D ~~ C DEC -‘ç 1979 DESIGN OF A PROGRAN FOR EXPERT DIAGNOSIS OF ACID BASE MID ELECTROLYTE DISTURBANCES ~979 Ratuesh S. Path LIBRA Rya- 4

Biodegradable Photo-Crosslinked Thin Polymer Networks Based on Vegetable Oil Hydroxyfatty Acids

USDA-ARS?s Scientific Manuscript database

Novel crosslinked thin polymer networks based on vegetable oil hydroxyfatty acids (HFAs) were prepared by UV photopolymerization and their mechanical properties were evaluated. Two raw materials, castor oil and 7,10-dihydroxy-8(E)-octadecenoic acid (DOD) were used as sources of mono- and di-HFAs, r...

Phase II Study of Neoadjuvant Anthracycline-Based Regimens Combined With Nanoparticle Albumin-Bound Paclitaxel and Trastuzumab for Human Epidermal Growth Factor Receptor 2-Positive Operable Breast Cancer.

PubMed

Tanaka, Satoru; Iwamoto, Mitsuhiko; Kimura, Kosei; Matsunami, Nobuki; Morishima, Hirotaka; Yoshidome, Katsuhide; Nomura, Takashi; Morimoto, Takashi; Yamamoto, Daigo; Tsubota, Yu; Kobayashi, Toshihiro; Uchiyama, Kazuhisa

2015-06-01

We treated patients with operable human epidermal growth factor receptor 2-positive breast cancer with neoadjuvant anthracycline regimens followed by nanoparticle albumin-bound paclitaxel plus trastuzumab. Of the 44 patients, 49% achieved a pathologic complete response (pCR). The pCR rate was 36% and 71% in the patients with estrogen receptor-positive and -negative cancer, respectively. Neoadjuvant therapy using this combination appears to be effective and safe. Introduction: Neoadjuvant chemotherapy plus trastuzumab. Neoadjuvant chemotherapy plus trastuzumab results in a 30% to 50% pathologic complete response (pCR) rate in human epidermal growth factor receptor 2 (HER2)-positive breast cancer and has been associated with improved therapeutic outcomes. Thus, the pCR rate can be useful in evaluating novel agents in this patient population. Nanoparticle albumin-bound (nab)-paclitaxel (PTX) can reduce the toxicity of PTX while maintaining its efficacy. The present study evaluated the activity and safety of nab-PTX as a neoadjuvant treatment of HER2(+) breast cancer. We treated patients with stage I to IIIA breast cancer using neoadjuvant epirubicin/cyclophosphamide (EC) or 5-fluorouracil/epirubicin/cyclophosphamide every 3 weeks (q3w) for 4 cycles, followed by nab-PTX (260 mg/m(2)) plus trastuzumab q3w for 4 cycles. The primary endpoint was the pCR rate. The secondary endpoints included the clinical response rate, disease-free survival, pathologic response rate (defined as pCR or minimal residual invasive disease only in the breast), breast-conserving surgery rate, and safety. Forty-six patients were enrolled. One patient met the exclusion criteria because of the coexistence of another malignant disease; therefore, we evaluated 45 patients in the entire study. One patient experienced rapid disease progression during EC therapy, leaving 44 patients evaluable for nab-PTX treatment. Of the 45 patients, 49% achieved a pCR. The pCR rate was 36% and 71% in those with

Increments to chiral recognition facilitating enantiomer separations of chiral acids, bases, and ampholytes using Cinchona-based zwitterion exchanger chiral stationary phases.

PubMed

Wernisch, Stefanie; Pell, Reinhard; Lindner, Wolfgang

2012-07-01

The intramolecular distances of anion and cation exchanger sites of zwitterionic chiral stationary phases represent potential tuning sites for enantiomer selectivity. In this contribution, we investigate the influence of alkanesulfonic acid chain length and flexibility on enantiomer separations of chiral acids, bases, and amphoteric molecules for six Cinchona alkaloid-based chiral stationary phases in comparison with structurally related anion and cation exchangers. Employing polar-organic elution conditions, we observed an intramolecular counterion effect for acidic analytes which led to reduced retention times but did not impair enantiomer selectivities. Retention of amphoteric analytes is based on simultaneous double ion pairing of their charged functional groups with the acidic and basic sites of the zwitterionic selectors. A chiral center in the vicinity of the strong cation exchanger site is vital for chiral separations of bases. Sterically demanding side chains are beneficial for separations of free amino acids. Enantioseparations of free (un-derivatized) peptides were particularly successful in stationary phases with straight-chain alkanesulfonic acid sites, pointing to a beneficial influence of more flexible moieties. In addition, we observed pseudo-enantiomeric behavior of quinine and quinidine-derived chiral stationary phases facilitating reversal of elution orders for all analytes. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fatty acid synthesis in Escherichia coli and its applications towards the production of fatty acid based biofuels

PubMed Central

2014-01-01

The idea of renewable and regenerative resources has inspired research for more than a hundred years. Ideally, the only spent energy will replenish itself, like plant material, sunlight, thermal energy or wind. Biodiesel or ethanol are examples, since their production relies mainly on plant material. However, it has become apparent that crop derived biofuels will not be sufficient to satisfy future energy demands. Thus, especially in the last decade a lot of research has focused on the production of next generation biofuels. A major subject of these investigations has been the microbial fatty acid biosynthesis with the aim to produce fatty acids or derivatives for substitution of diesel. As an industrially important organism and with the best studied microbial fatty acid biosynthesis, Escherichia coli has been chosen as producer in many of these studies and several reviews have been published in the fields of E. coli fatty acid biosynthesis or biofuels. However, most reviews discuss only one of these topics in detail, despite the fact, that a profound understanding of the involved enzymes and their regulation is necessary for efficient genetic engineering of the entire pathway. The first part of this review aims at summarizing the knowledge about fatty acid biosynthesis of E. coli and its regulation, and it provides the connection towards the production of fatty acids and related biofuels. The second part gives an overview about the achievements by genetic engineering of the fatty acid biosynthesis towards the production of next generation biofuels. Finally, the actual importance and potential of fatty acid-based biofuels will be discussed. PMID:24405789

Acid-base chemical reaction model for nucleation rates in the polluted atmospheric boundary layer.

PubMed

Chen, Modi; Titcombe, Mari; Jiang, Jingkun; Jen, Coty; Kuang, Chongai; Fischer, Marc L; Eisele, Fred L; Siepmann, J Ilja; Hanson, David R; Zhao, Jun; McMurry, Peter H

2012-11-13

Climate models show that particles formed by nucleation can affect cloud cover and, therefore, the earth's radiation budget. Measurements worldwide show that nucleation rates in the atmospheric boundary layer are positively correlated with concentrations of sulfuric acid vapor. However, current nucleation theories do not correctly predict either the observed nucleation rates or their functional dependence on sulfuric acid concentrations. This paper develops an alternative approach for modeling nucleation rates, based on a sequence of acid-base reactions. The model uses empirical estimates of sulfuric acid evaporation rates obtained from new measurements of neutral molecular clusters. The model predicts that nucleation rates equal the sulfuric acid vapor collision rate times a prefactor that is less than unity and that depends on the concentrations of basic gaseous compounds and preexisting particles. Predicted nucleation rates and their dependence on sulfuric acid vapor concentrations are in reasonable agreement with measurements from Mexico City and Atlanta.

Adipose‑derived stem cells and hyaluronic acid based gel compatibility, studied in vitro.

PubMed

Guo, Jiayan; Guo, Shu; Wang, Yuxin; Yu, Yanqiu

2017-10-01

Minimally invasive aesthetic and cosmetic procedures have increased in popularity. Injectable dermal fillers provide soft tissue augmentation, improve facial rejuvenation and wrinkles, and correct tissue defects. To investigate the use of adipose‑derived stem cells integrated with a hyaluronic acid based gel as a dermal filler, the present study used cytotoxicity studies, proliferation studies, adipogenic and osteogenic differentiation, apoptosis assays and scanning electron microscopy. Although hyaluronic acid induced low levels of apoptosis in adipose‑derived stem cells, its significantly promoted proliferation of adipose‑derived stem cells. Hyaluronic acid demonstrates little toxicity against adipose‑derived stem cells. Adipose‑derived stem cells were able to differentiate into adipocytes and osteoblasts. Furthermore, scanning electron microscopy revealed that adipose‑derived stem cells maintained intact structures on the surface of hyaluronic acid as well as in it, and demonstrated abundant cell attachments. The present study demonstrated the compatibility of adipose‑derived stem cells and hyaluronic acid based gels in vitro.

Geometric Patterns for Neighboring Bases Near the Stacked State in Nucleic Acid Strands.

PubMed

Sedova, Ada; Banavali, Nilesh K

2017-03-14

Structural variation in base stacking has been analyzed frequently in isolated double helical contexts for nucleic acids, but not as often in nonhelical geometries or in complex biomolecular environments. In this study, conformations of two neighboring bases near their stacked state in any environment are comprehensively characterized for single-strand dinucleotide (SSD) nucleic acid crystal structure conformations. An ensemble clustering method is used to identify a reduced set of representative stacking geometries based on pairwise distances between select atoms in consecutive bases, with multiple separable conformational clusters obtained for categories divided by nucleic acid type (DNA/RNA), SSD sequence, stacking face orientation, and the presence or absence of a protein environment. For both DNA and RNA, SSD conformations are observed that are either close to the A-form, or close to the B-form, or intermediate between the two forms, or further away from either form, illustrating the local structural heterogeneity near the stacked state. Among this large variety of distinct conformations, several common stacking patterns are observed between DNA and RNA, and between nucleic acids in isolation or in complex with proteins, suggesting that these might be stable stacking orientations. Noncanonical face/face orientations of the two bases are also observed for neighboring bases in the same strand, but their frequency is much lower, with multiple SSD sequences across categories showing no occurrences of such unusual stacked conformations. The resulting reduced set of stacking geometries is directly useful for stacking-energy comparisons between empirical force fields, prediction of plausible localized variations in single-strand structures near their canonical states, and identification of analogous stacking patterns in newly solved nucleic acid containing structures.

Base pairing and base mis-pairing in nucleic acids

NASA Technical Reports Server (NTRS)

Wang, A. H. J.; Rich, A.

1986-01-01

In recent years we have learned that DNA is conformationally active. It can exist in a number of different stable conformations including both right-handed and left-handed forms. Using single crystal X-ray diffraction analysis we are able to discover not only additional conformations of the nucleic acids but also different types of hydrogen bonded base-base interactions. Although Watson-Crick base pairings are the predominant type of interaction in double helical DNA, they are not the only types. Recently, we have been able to examine mismatching of guanine-thymine base pairs in left-handed Z-DNA at atomic resolution (1A). A minimum amount of distortion of the sugar phosphate backbone is found in the G x T pairing in which the bases are held together by two hydrogen bonds in the wobble pairing interaction. Because of the high resolution of the analysis we can visualize water molecules which fill in to accommodate the other hydrogen bonding positions in the bases which are not used in the base-base interactions. Studies on other DNA oligomers have revealed that other types of non-Watson-Crick hydrogen bonding interactions can occur. In the structure of a DNA octamer with the sequence d(GCGTACGC) complexed to an antibiotic triostin A, it was found that the two central AT base pairs are held together by Hoogsteen rather than Watson-Crick base pairs. Similarly, the G x C base pairs at the ends are also Hoogsteen rather than Watson-Crick pairing. Hoogsteen base pairs make a modified helix which is distinct from the Watson-Crick double helix.