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PubMed1979

The effect of cyclophosphamide on a secondary ocular immune response in rabbits.

Treatment of rabbits with immunosuppressive doses of cyclophosphamide during the primary response to intravitreally injected bovine gamma globulin did not prevent priming for a secondary response to the same antigen. High antibody titers were found in the aqueous humor and serum of most of the treated rabbits. Ocular tissue plaque forming cell numbers were similar to those of the controls in many of the rabbits, and slightly lower in others. Treatment with cyclophosphamide completely suppressed the ocular immune response in many rabbits that had undergone a primary response following intravitreal injection of BGC. The response in other animals was depressed but not completely inhibited. The presence of ocular inflammation and lymphocytes in the challenged eyes of the treated rabbits suggested a differential effect of cyclophosphamide on cells stimulated to divide after challenge.

Animals↗
PubMed1990

Bone formation in porous implants of delrin and commercially pure titanium.

Clinicians have been using implants made by titanium or delrin with varying results. In this study dividable implants, bone growth chambers (BGC), of titanium and delrin were inserted into the rabbit tibia. The ingrowth of hard tissue into a canal in the implant was evaluated after 3 weeks by microradiography and numerically determined by computer analysis. Results showed that bone ingrowth into titanium implants was significantly larger than into delrin implants (P less than 0.005). The possible reasons for this are discussed.

Animals↗
PubMed2005

Mapping and modeling the biogeochemical cycling of turf grasses in the United States.

Turf grasses are ubiquitous in the urban landscape of the United States and are often associated with various types of environmental impacts, especially on water resources, yet there have been limited efforts to quantify their total surface and ecosystem functioning, such as their total impact on the continental water budget and potential net ecosystem exchange (NEE). In this study, relating turf grass area to an estimate of fractional impervious surface area, it was calculated that potentially 163,800 km2 (+/- 35,850 km2) of land are cultivated with turf grasses in the continental United States, an area three times larger than that of any irrigated crop. Using the Biome-BGC ecosystem process model, the growth of warm-season and cool-season turf grasses was modeled at a number of sites across the 48 conterminous states under different management scenarios, simulating potential carbon and water fluxes as if the entire turf surface was to be managed like a well-maintained lawn. The results indicate that well-watered and fertilized turf grasses act as a carbon sink. The potential NEE that could derive from the total surface potentially under turf (up to 17 Tg C/yr with the simulated scenarios) would require up to 695 to 900 liters of water per person per day, depending on the modeled water irrigation practices, suggesting that outdoor water conservation practices such as xeriscaping and irrigation with recycled waste-water may need to be extended as many municipalities continue to face increasing pressures on freshwater.

Carbon↗
PubMed1999

The impact of growing-season length variability on carbon assimilation and evapotranspiration over 88 years in the eastern US deciduous forest

Recent research suggests that increases in growing-season length (GSL) in mid-northern latitudes may be partially responsible for increased forest growth and carbon sequestration. We used the BIOME-BGC ecosystem model to investigate the impacts of including a dynamically regulated GSL on simulated carbon and water balance over a historical 88-year record (1900-1987) for 12 sites in the eastern USA deciduous broadleaf forest. For individual sites, the predicted GSL regularly varied by more than 15 days. When grouped into three climatic zones, GSL variability was still large and rapid. There is a recent trend in colder, northern sites toward a longer GSL, but not in moderate and warm climates. The results show that, for all sites, prediction of a long GSL versus using the mean GSL increased net ecosystem production (NEP), gross primary production (GPP), and evapotranspiration (ET); conversely a short GSL is predicted to decrease these parameters. On an absolute basis, differences in GPP between the dynamic and mean GSL simulations were larger than the differences in NEP. As a percentage difference, though, NEP was much more sensitive to changes in GSL than were either GPP or ET. On average, a 1-day change in GSL changed NEP by 1.6%, GPP by 0.5%, and ET by 0.2%. Predictions of NEP and GPP in cold climates were more sensitive to changes in GSL than were predictions in warm climates. ET was not similarly sensitive. First, our results strongly agree with field measurements showing a high correlation between NEP and dates of spring growth, and second they suggest that persistent increases in GSL may lead to long-term increases in carbon storage.

Journal Article↗
PubMed2025

Gene amir_2071 of Actinosynnema mirum DSM 43827 encodes a dimethylallyltryptophan synthase superfamily protein responsible for the production of prenylated tyrosine.

Actinosynnema mirum DSM 43827 is a bacterium from the small genus Actinosynnema within the rapidly growing actinomycete family Pseudonocardiaceae (Land M et al. Stand Genomic Sci 1:46-53 2009). Despite its diverse repertoire of specialized metabolite biosynthetic gene clusters (BGCs), the potential of A. mirum for production of bioactive molecules is not fully explored. Here, we used a heterologous expression approach to gain deeper insight into this issue. In this work we report that expression of in silico predicted BGC#4 from A. mirum in S. albus Del14 and S. lividans ΔYA9 led to production of several prenylated derivatives of tyrosine. Their most likely structures, according to MS and MS/MS data, agreed with 4-O-prenyl-(L)-tyrosine and its N-acetyl derivative, previously described in lichen-forming fungi (Iacovelli R et al. J Nat Prod 87:2243-2254 2024). Further experiments confirm the production of the aforementioned compounds is governed by a single structural gene, amir_2071 for prenyltransferase of dimethylallyltryptophan synthase (DMATS) superfamily, whose homologs are abundant in bacterial genomes.

Tyrosine↗
PubMed2026

Comparative Genomics of Paenibacillus Secondary Metabolism: Unveiling the Putative Biosynthetic Gene Cluster for Paenialvins in Paenibacillus Alvei Strain 32.

In this study, we used comparative genomics and culture-based methods to investigate Biosynthetic Gene Clusters (BGCs) responsible for the production of antimicrobial peptides. Paenibacillus alvei strain 32 was isolated from a cystic fibrosis sputum. Its genome was sequenced using Illumina, showing a size of 6,584,590 bp with 239 contigs assembled in 26 scaffolds, an average coverage of 243X, and 6,832 coding sequences. ANI analysis and in silico DNA-DNA hybridization showed its affiliation inside Paenibacillus alvei, with a clear separation from other related strains, leading us to propose a distinct species-level genomic clade (genomospecies) within this group. AntiSMASH analysis predicted 22 putative BGCs in the genome of strain 32. Its culture supernatant exhibited inhibitory activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), Bacillus cereus, and Enterococcus faecalis. By comparing in silico BGC predictions with activities described in the literature, we propose that strain 32 harbours a specific 110-kb cluster (cluster 6.2) with five non-ribosomal peptide synthetase (NRPS) genes. These synthetases are predicted to direct the assembly of a 16-amino acid backbone that correlates with the structure of paenialvins, which are known anti-MRSA molecules. This study describes the putative biosynthetic pathway of the paenialvins and explains structural variations, bringing useful data on Paenibacillus secondary metabolism for future antibiotic development.

Paenibacillus alvei↗
PubMed2026

Integrated Genome Mining and Bioactivity-Guided Isolation of Antimicrobial Peptides from Bacillus amyloliquefaciens BS4.

Bacterial resistance remains a critical global health challenge, driving the continuous search for novel antimicrobial agents. Bacillus amyloliquefaciens is a recognized repository of bioactive metabolites; however, its full biosynthetic potential requires integrated genomic and experimental validation. This study characterized the antimicrobial profile of B. amyloliquefaciens BS4 through a hybrid pipeline. Genome sequencing and de novo assembly revealed a 3.9 Mb chromosome with a G + C content of 46.14%. Functional annotation identified 3,887 coding sequences, including pathways for siderophore biosynthesis and a complete bacilysin biosynthetic cluster. BGC analysis using antiSMASH v7.1.0 and BAGEL4 identified 18 biosynthetic gene clusters, while similarity network analysis via BiG-SCAPE highlighted unique singleton BGCs, indicating untapped biosynthetic diversity. Although in silico screening via Macrel predicted two putative cationic antimicrobial peptides (AMPs), bioactivity-guided purification utilizing sequential RP-HPLC, and de novo sequencing revealed a distinct set of four active peptides. Notably, three of these sequences were identified as fragments derived from the BclA exosporium protein family, highlighting the structural proteome as a non-canonical source of antimicrobials. The purified fractions exhibited activity against M. luteus and E. coli, while displaying no significant hemolytic activity or cytotoxicity, even above the MIC values. Molecular docking further supported the interaction of these candidates with bacterial targets. Overall, this hybrid strategy effectively uncovers the antimicrobial complexity of BS4, revealing 'cryptic' peptide candidates with therapeutic potential.

Bacillus amyloliquefaciens BS4↗
PubMed2004

Cytotoxic isoprenylated xanthones from Cudrania tricuspidata.

Eight new isoprenylated xanthones, cudratricusxanthones A-H (1-8), were isolated from the roots of Cudrania tricuspidata, together with ten known compounds, cudraxanthones H (9) and M (10), xanthone V(1a) (11), toxyloxanthone C (12), macluraxanthone B (13), 1-hydroxy-3, 6, 7-trimethoxyxanthone (14), cycloartocarpesin (15), artocarpesin (16), cudraflavone B (17), and kaempferol (18). Their structures were characterized by spectroscopic methods. Xanthones 5, 7, 10, and 12 showed inhibitory effects on four kinds of human digestive apparatus tumor cell lines (HCT-116, SMMC-7721, SGC-7901, and BGC-823) with IC(50) values of 1.6-11.8 microg/mL. Xanthones 2, 4, and 11 displayed significant cytotoxicity against HCT-116, SMMC-7721, and SGC-7901 (IC(50)=1.3-9.8 microg/mL). Flavonoids 15-17 were almost inactive.

Antineoplastic Agents↗
PubMed2006

Synthesis, characterization and biological activity of complexes of lanthanum(III) with 2-(1'-phenyl- 2'-carboxyl-3'-aza-n-butyl)-1,10-phenanthroline and 2-(1'-p-phenol-2'-carboxyl-3'-aza-n-butyl)-1,10-phenanthroline.

Two novel ligands 2-(1'-phenyl-2'-carboxyl-3'-aza-n-butyl)-1,10-phenanthroline (L1) and 2-(1'-p-phenol-2'-carboxyl-3'-aza-butyl)-1,10-phenanthroline (L2), and their La(III) complexes of La(III)L1, La(III)(L1)(2), La(III)L2, and La(III)(L2)(2), were synthesized and characterized by (1)H NMR, elemental analysis, IR, thermal analysis and conductance measurement. All complexes have been assayed for anticancer activity in vitro against HL-60 (human leukocytoma) cells, PC-3MIE8 (human prostate carcinoma) cells, BGC-823 (human stomach carcinoma) cells, MDA-MB-435 (human galactophore carcinoma) cells, Bel-7402 (human liver carcinoma) cells, and HeLa (human cervix carcinoma) cells. Results showed that the two complexes La(III)L1 and La(III)(L1)(2) exhibited good cytotoxic activity against different cell lines in general; and La(III)(L1)(2) is more effective than cisplatin against all six cell lines. DNA-binding studies indicated that, besides the intercalation, the complexes bind to DNA by the other interaction(s).

Aza Compounds↗
PubMed2005

Novel peptide derivatives of bleomycin A5: synthesis, antitumor activity and interaction with DNA.

A series of novel amino acid and peptide derivatives of bleomycin (BLM) A(5) were synthesized. All the compounds possessed significant antitumor activities in vitro against HL-60, BGC-823, PC-3MIE8, and MDA-MB-435 cell lines. Their antitumor activities against MDA-MB-435 were 10-fold higher than BLM A5. The DNA cleavage studies indicated that the hydrophobic amino acid or peptide derivatives of BLM A5 could induce higher cleavage ratio of double to single strand DNA than BLM A5. From the DNA binding studies, we found that the derivatives containing either D-conformation amino acid or basic amino acid could facilitate DNA binding of BLM.

Antineoplastic Agents↗
PubMed2005

Effects of ATRA on expression of mRNA binding protein p62 in human gastric cancer cells.

The distribution of the cancer-associated protein p62 in human gastric carcinoma (BGC-823) cells was examined by confocal laser scanning microscopy and electron microscope immunocytochemistry. In control cells p62 was cytoplasmic in location and concentrated in the cytoplasmic matrix, but when cell growth was inhibited by treatment with 50 microM all-trans-retinoic acid (ATRA) for 5 days, p62 expression decreased and the protein was translocated from cytoplasm to nucleus. Ultrastructural localization using gold particles showed that p62 was bond mainly to a linear structure in nucleus. The speculation that p62 binds Insulin-like growth factor (IGF)-II mRNA indicates its probable involvement in the posttranscriptional IGF-II mRNA processing and p62 could play a role in tumorgenesis by regulating the expression of IGF-II. Further studies will be needed to confirm this view.

Carcinoma↗
PubMed2006

High frequency occurrence of 1-OPRD variant of PRNP gene in gastric cancer cell lines and Chinese population with gastric cancer.

The prion protein gene PRNP encodes PrPc and PrPsc, causing a number of neurological disorders. Approximately 10-15% of human prion disease is inherited and more than 20 pathogenic mutations have been found. Most of the genetic alterations are point mutations, with the exception of genetic insertions of one to nine extra octapeptide repeats occurring in the important octapeptide-coding region. Our previous work showed that PrPc was overexpressed in gastric cancer. We wondered whether mutations of PrPc existed in human gastric cancer. DNA sequencing and gel electrophoresis were used to determine the possible mutation of PrPc in patients and cell lines of gastric cancer. We found that 1-OPRD (one octapeptide-repeat deletion) homozygosity or heterozygosity exists in several gastric cancer cell lines, e.g. MKN28 and KatoIII are homozygous for 1-OPRD, and SGC7901 and BGC-823 are heterozygous for 1-OPRD. The mutation frequency in tissues of gastric cancer cases is significantly higher than that in the common population (p<0.05). All positive cases in gastric cancer were found to be heterozygous for 1-OPRD. Further study of the variant may be helpful in understanding the mechanisms of occurrence and development of clinical gastric carcinoma as well as the biology of the mysterious gene PRNP.

Adolescent↗
PubMed2005

Synthesis and in vitro cytotoxic evaluation of 1,3-bisubstituted and 1,3,9-trisubstituted beta-carboline derivatives.

A series of novel 1,3-bisubstituted and 1,3,9-trisubstituted beta-carboline derivatives was synthesized from the starting material l-tryptophan. Cytotoxic activities of these compounds were investigated in vitro. The results showed that 1,3,9-trisubstituted beta-carboline derivatives had higher cytotoxic activities in vitro than the corresponding 1,3-bisubstituted compounds. Among all the synthesized 1,3,9-trisubstituted beta-carboline derivatives, the compounds with a methyl substituent at position-1 displayed more potent cytotoxic activities, furthermore compound 5e having an ethoxycarbonyl substituent at position-3 and a pentafluorobenzyl at position-9, respectively, was found to be the most potent compounds of this series with IC(50) value of 4 uM against BGC-823 cell lines. These data suggested that (1) the cytotoxic potencies of beta-carboline derivatives were enhanced by the introduction of appropriate substituents into position-1 and position-9 in beta-carboline; (2) the beta-carboline structure might be an important basis for the design and synthesis of new antitumor drugs; (3) the methyl substituent at position-1, the pentafluorobenzyl group at position-9 and the ethoxycarbonyl substituent at position-3 were the optimal combination for the improvement of cytotoxic activity of the beta-carboline derivatives.

Carbolines↗
PubMed2005

The cytotoxic activity of ursolic acid derivatives.

Ursolic acid and 2alpha-hydroxyursolic acid isolated from apple peels were found to show growth inhibitory activity against four tumor cell lines, HL-60, BGC, Bel-7402 and Hela. Structural modifications were performed on the C-3, C-28 and C-11 positions of ursolic acid and the cytotoxicity of the derivatives was evaluated. The SAR revealed that the triterpenes possessing two hydrogen-bond forming groups (an H-donor and a carbonyl group) at positions 3 and 28 exhibit cytotoxic activity. The configuration at C-3 was found to be important for the activity. Introduction of an amino group increased the cytotoxicity greatly. A 3beta-amino derivative was 20 times more potent than the parent ursolic acid. The 28-aminoalkyl dimer compounds showed selective cytotoxicity.

Antineoplastic Agents, Phytogenic↗
PubMed2006

Synthesis, cytotoxicity and DNA-binding levels of ammine/propylamine platinum(II) complexes with carboxylates.

Seven new mixed ammine/propylamine platinum(II) complexes with carboxylates (a-g) have been synthesized and characterized by elemental analysis, conductivity, IR, UV, and (1)H NMR spectra techniques. The cytotoxicity of these complexes was tested by MTT assay. The levels of total platinum bound to DNA were measured by ICP-MS. The results indicate that the complexes (a-g) have better cytotoxicity against EJ and HL-60 than other carcinoma cell lines. The cytotoxicity increases in the sequence: g<f<e<d<b<c<a against tested carcinoma cell lines. The cytotoxicity of complexes (a-c) is equal to that of cisplatin against HL-60. The cytotoxicity of complex a is also equal to that of cisplatin against EJ. However, the complexes (a-g) are significantly less potent than cisplatin against BGC-823, HCT-8 and MCF-7. The total DNA-platination levels increase in the sequence: cisplatin<g<e<f<d<b<c<a under the same experimental conditions. It suggests that there is no correlation between total DNA-platination levels in HL-60 cells and cytotoxicity of ammine/propylamine platinum complexes. When leaving groups are aromatic carboxylates, the complexes have better cytotoxicity, and moreover, the substituent in benzene ring also influences cytotoxicity.

Amines↗
PubMed2005

Synthesis, crystal structure, cytotoxic activity and DNA-binding properties of the copper (II) and zinc (II) complexes with 1-[3-(2-pyridyl)pyrazol-1-ylmethyl]naphthalene.

A new ligand L, 1-[3-(2-pyridyl)pyrazol-1-ylmethyl]naphthalene, and its two metal complexes, [Cu(L)3](ClO4)2 (1) and [Zn(L)3](ClO4)2(H2O)2 (2), have been synthesized and characterized. The crystal structure of complex 1 was determined by single crystal X-ray diffraction, which crystallized in monoclinic, space group P2(1)/n with unit cell parameters, a = 12.710(4) angstroms, b = 12.135(3) angstroms, c = 33.450(9) angstroms, beta = 93.281(5) degrees and Z = 4. The Cu atom was six-coordinated to N(1), N(2), N(4), N(5), N(7) and N(8) from three L ligands and formed a slightly distorted octahedral geometry. Complexes 1 and 2, and ligand L were subjected to biological tests in vitro using three different cancer cell lines (HL-60, BGC-823 and MDA-MB-435). Complex 1 showed significant cytotoxic activity against three cancer cell lines. The interactions of complexes 1 and 2, and ligand L with calf thymus DNA were then investigated by thermal denaturation, viscosity measurements and spectrophotometric methods. The experimental results indicated that complexes 1 and 2 bound to DNA by intercalative mode via the ligand L. The intrinsic binding constants of complexes 1 and 2, and ligand L with DNA were 1.8 x 10(4), 5.4 x 10(3) and 2.76 x 10(3) M(-1), respectively.

Animals↗
PubMed2005

Simulating effects of fire disturbance and climate change on boreal forest productivity and evapotranspiration.

We used a terrestrial ecosystem process model, BIOME-BGC, to investigate historical climate change and fire disturbance effects on regional carbon and water budgets within a 357,500 km(2) portion of the Canadian boreal forest. Historical patterns of increasing atmospheric CO2, climate change, and regional fire activity were used as model drivers to evaluate the relative effects of these impacts to spatial patterns and temporal trends in forest net primary production (NPP) and evapotranspiration (ET). Historical trends of increasing atmospheric CO2 resulted in overall 13% and 5% increases in annual NPP and ET from 1994 to 1996, respectively. NPP was found to be relatively sensitive to changes in air temperature (T(a)), while ET was more sensitive to precipitation (P) change within the ranges of observed climate variability (e.g., +/-2 degrees C for T(a) and +/-20% for P). In addition, the potential effect of climate change related warming on NPP is exacerbated or offset depending on whether these changes are accompanied by respective decreases or increases in precipitation. Historical fire activity generally resulted in reductions of both NPP and ET, which consumed an average of approximately 6% of annual NPP from 1959 to 1996. Areas currently occupied by dry conifer forests were found to be subject to more frequent fire activity, which consumed approximately 8% of annual NPP. The results of this study show that the North American boreal ecosystem is sensitive to historical patterns of increasing atmospheric CO2, climate change and regional fire activity. The relative impacts of these disturbances on NPP and ET interact in complex ways and are spatially variable depending on regional land cover and climate gradients.

Canada↗
PubMed1984

The neuronal organization of the outer plexiform layer of the primate retina.

In the primate retina at the level of the first synapse in the visual system, the outer plexiform layer, processes from 15 different types of neurons have so far been described. These are the synaptic spherules of rods, the pedicles of three spectral types of cones, dendrites and axons of two types of horizontal cell, dendrites of seven types of bipolar cell, processes of interplexiform cells, and the outwardly coursing dendritic extensions of biplexiform ganglion cells. The interconnections of these neurons as studied by electron microscopy and Golgi-EM are presented in a summary diagram (Fig. 27). Basal processes from cone pedicles contact the cone pedicles, and rod spherules forming gap junctions. The dendrites of both types of horizontal cell (hI and hII) connect only to cone pedicles and form lateral elements of triads at the ribbon synaptic complex. The HI axon terminals end as lateral elements at rod spherules while the axons of HII horizontal cells connect with cones in a manner similar to their dendrites. Interplexiform cells (ipc) do not contact either rod or cone synaptic endings. Rod bipolar cell (rb) dendrites end as central elements at the ribbon synaptic complex of rod spherules. The dendrites of flat midget (fm), flat top (fb), and giant bistratified bipolar (gb) cells all form basal junctions with cone pedicles. Ending as central elements of triads at cone pedicles are the dendrites of invaginating midget (im), diffuse invaginating cone (ib), and blue-cone (bb) bipolar cells. Biplexiform ganglion cells (bgc) connect to rods as central elements opposite the synaptic ribbon in the spherules. As compared to an earlier summary diagram of the outer plexiform layer (Kolb, 1970), the primate retina is now known not to be as simply organized as was once thought. Although our knowledge of the types of neurons contributing processes to this first synaptic layer, and the nature of their connections with other neurons has been broadened, especially within the past few years, this summary diagram is not intended to represent the complete or final "picture." Undoubtedly, future investigations along the lines of research outlined here will provide additional details to this wiring diagram so that we may better understand the processing of visual information by neurons in the retina.

Animals↗