bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interactions between Diatoms and Bacteria
Authors: Amin Shady A. , Parker Micaela S. , Armbrust E. Virginia 
Published: August 2012

SUMMARY
Diatoms and bacteria have cooccurred in common habitats for hundreds of millions of years, thus fostering specific associations and interactions with global biogeochemical consequences. Diatoms are responsible for one-fifth of the photosynthesis on Earth, while bacteria remineralize a large portion of this fixed carbon in the oceans. Through their coexistence, diatoms and bacteria cycle nutrients between oxidized and reduced states, impacting bioavailability and ultimately feeding higher trophic levels. Here we present an overview of how diatoms and bacteria interact and the implications of these interactions. We emphasize that heterotrophic bacteria in the oceans that are consistently associated with diatoms are confined to two phyla. These consistent bacterial associations result from encounter mechanisms that occur within a microscale environment surrounding a diatom cell. We review signaling mechanisms that occur in this microenvironment to pave the way for specific interactions. Finally, we discuss known interactions between diatoms and bacteria and exciting new directions and research opportunities in this field. Throughout the review, we emphasize new technological advances that will help in the discovery of new interactions. Deciphering the languages of diatoms and bacteria and how they interact will inform our understanding of the role these organisms have in shaping the ocean and how these interactions may change in future oceans.
Biogenesis of the Saccharomyces cerevisiae Pheromone
a
-Factor, from Yeast Mating to Human Disease
Authors: Michaelis Susan , Barrowman Jemima 
Published: August 2012

SUMMARY

The mating pheromone
a
-factor secreted by
Saccharomyces cerevisiae
is a farnesylated and carboxylmethylated peptide and is unusually hydrophobic compared to other extracellular signaling molecules. Mature
a
-factor is derived from a precursor with a C-terminal CAAX motif that directs a series of posttranslational reactions, including prenylation, endoproteolysis, and carboxylmethylation. Historically,
a
-factor has served as a valuable model for the discovery and functional analysis of CAAX-processing enzymes. In this review, we discuss the three modules comprising the
a
-factor biogenesis pathway: (i) the C-terminal CAAX-processing steps carried out by Ram1/Ram2, Ste24 or Rce1, and Ste14; (ii) two sequential N-terminal cleavage steps, mediated by Ste24 and Axl1; and (iii) export by a nonclassical mechanism, mediated by the ATP binding cassette (ABC) transporter Ste6. The small size and hydrophobicity of
a
-factor present both challenges and advantages for biochemical analysis, as discussed here. The enzymes involved in
a
-factor biogenesis are conserved from yeasts to mammals. Notably, studies of the zinc metalloprotease Ste24 in
S. cerevisiae
led to the discovery of its mammalian homolog ZMPSTE24, which cleaves the prenylated C-terminal tail of the nuclear scaffold protein lamin A. Mutations that alter ZMPSTE24 processing of lamin A in humans cause the premature-aging disease progeria and related progeroid disorders. Intriguingly, recent evidence suggests that the entire
a
-factor pathway, including all three biogenesis modules, may be used to produce a prenylated, secreted signaling molecule involved in germ cell migration in
Drosophila
. Thus, additional prenylated signaling molecules resembling
a
-factor, with as-yet-unknown roles in metazoan biology, may await discovery.
The Multiple Functions of TRBP, at the Hub of Cell Responses to Viruses, Stress, and Cancer
Authors: Daniels Sylvanne M. , Gatignol Anne 
Published: August 2012

SUMMARYThe TAR RNA binding protein (TRBP) has emerged as a key player in many cellular processes. First identified as a cellular protein that facilitates the replication of human immunodeficiency virus, TRBP has since been shown to inhibit the activation of protein kinase R (PKR), a protein involved in innate immune responses and the cellular response to stress. It also binds to the PKR activator PACT and regulates its function. TRBP also contributes to RNA interference as an integral part of the minimal RNA-induced silencing complex with Dicer and Argonaute proteins. Due to its multiple functions in the cell, TRBP is involved in oncogenesis when its sequence is mutated or its expression is deregulated. The depletion or overexpression of TRBP results in malignancy, suggesting that the balance of TRBP expression is key to normal cellular function. These studies show that TRBP is multifunctional and mediates cross talk between different pathways. Its activities at the molecular level impact the cellular function from normal development to cancer and the response to infections.
DNA Repair and Genome Maintenance in Bacillus subtilis
Authors: Lenhart Justin S. , Schroeder Jeremy W. , Walsh Brian W. , Simmons Lyle A. 
Published: August 2012

SUMMARY

From microbes to multicellular eukaryotic organisms, all cells contain pathways responsible for genome maintenance. DNA replication allows for the faithful duplication of the genome, whereas DNA repair pathways preserve DNA integrity in response to damage originating from endogenous and exogenous sources. The basic pathways important for DNA replication and repair are often conserved throughout biology. In bacteria, high-fidelity repair is balanced with low-fidelity repair and mutagenesis. Such a balance is important for maintaining viability while providing an opportunity for the advantageous selection of mutations when faced with a changing environment. Over the last decade, studies of DNA repair pathways in bacteria have demonstrated considerable differences between Gram-positive and Gram-negative organisms. Here we review and discuss the DNA repair, genome maintenance, and DNA damage checkpoint pathways of the Gram-positive bacterium
Bacillus subtilis.
We present their molecular mechanisms and compare the functions and regulation of several pathways with known information on other organisms. We also discuss DNA repair during different growth phases and the developmental program of sporulation. In summary, we present a review of the function, regulation, and molecular mechanisms of DNA repair and mutagenesis in Gram-positive bacteria, with a strong emphasis on
B. subtilis.
Sexually transmitted penile amoebiasis in Iran: a case series
Authors: Abdolrasouli Alireza , de Vries Henry J C , Hemmati Yahya , Roushan Azita , Hart Jason , Waugh Michael Anthony 
Published: August 2012

ObjectivesFour cases of penile amoebiasis (PA) presenting as genital ulceration seen among men who practiced unprotected insertive anal intercourse in Tehran are described.MethodsPA was confirmed by observation of motile trophozoites ofEntamoeba histolyticafrom lesions examined by wet mount microscopy.ResultsUlcers were solitary, painful, irregular, discharging and increasing in size. Three heterosexuals and one bisexual had practised insertive anal intercourse in the 2 weeks before diagnosis. Bilateral inguinal lymphadenitis occurred in one case. Direct examination of lesions was positive for the presence of amoebic trophozoites. Complete resolution occurred after treatment with oral metronidazole 800 mg three times daily for 7–10 days.ConclusionsClinicians need to be aware of cutaneous amoebiasis in sexually active men who practice unprotected insertive anal sex where intestinal amoebiasis is endemic. Wet mount microscopy is a rapid and useful diagnostic test.
External infections contribute minimally to HIV incidence among HIV sero-discordant couples in sub-Saharan Africa
Authors: Chemaitelly Hiam , Abu-Raddad Laith J 
Published: August 2012

ObjectiveRecent randomised clinical trials among stable HIV sero-discordant couples (SDCs) in sub-Saharan Africa (SSA) have reported that about 20–30% of new HIV infections are acquired from external sexual partners, rather than transmitted from the infected to the uninfected partner within the couple. The aim of this study is to examine whether, and to what extent, these findings are generalisable to SDCs in the wider population in SSA.MethodsA mathematical model was constructed to calculate the fraction of new HIV-1 infections among SDCs that are due to sources external to the couple. The model was parameterised using empirical and population-based data for 20 countries in SSA. Uncertainty and sensitivity analyses were also conducted.ResultsThe contribution of external infections among SDCs was generally modest, but it varied widely across SSA. In low HIV prevalence countries (≤3.0%), it ranged from 0.6–2.9%. In intermediate prevalence countries (3.0–18.0%), it ranged from 4.9–11.7%. In Swaziland and Lesotho, the world's most-intense epidemics, sizable levels of 27.9% and 27.3% were found, respectively.ConclusionsIn most countries in SSA, nearly all HIV acquisitions by the uninfected partners in SDCs appear to be due to transmissions from the HIV infected partners in the SDCs. The contribution of externally acquired infections varies with HIV population prevalence, but rarely exceeds 10% in the majority of countries. Only in hyperendemic HIV epidemics the contribution of external infections is substantial and may reach the levels reported in recent randomised clinical trials involving SDCs.
Seed dynamics of two fire-dependent Geranium species in the boreal forest of southeastern Sweden
Authors: Risberg Lotta , Granström Anders 
Published: August 2012

We analyzed critical life-history variables for two rare fire-dependent annual Geranium species in southern Sweden, which are today threatened because of effective fire suppression. At recently burned sites with abundant recruitment, seedlings occurred only where the humus layer had been completely removed by smoldering fire. Emergence depths ranged 1–6 cm in the mineral soil. Soil sampling at four sites revealed that in unburned soil Geranium seeds were located only in the mineral soil. Surprisingly, residual seeds were still present where fire had burned away the humus layer. An experiment showed that both species deposit seeds relatively evenly within a radius of 5–6 m, through ballistic dispersal. Repeated sampling in the field over a 2-year period after seed dispersal at one site indicated a low rate of seed depletion, corroborated by an indoor incubation of seeds. Our results show that successful management of these species depend on deep-burning prescribed fire, which can only result after severe drought. On the other hand, the seed bank is extremely long-lived, as viable seeds were present at a site last burned 200 years ago. This well-protected seed bank will likely buffer against both ill-timed fires and occasional failure in the recruiting seedling populations.
New Strategies in Sarcoma Therapy: Linking Biology and Novel Agents
Authors: Janeway Katherine A. , Maki Robert G. 
Published: August 2012

Abstract
The ability to better interrogate the genetic state of a given cancer is giving rise to a new paradigm in cancer therapeutics in which the specific genetic alterations that give rise to the cancer inform the therapeutic decision-making for that specific patient. Sarcomas of soft tissue and bone represent model diseases that underscore this paradigm. However, many barriers prevent linkage of one of the 75 or more different types of sarcoma to novel therapeutic agents. In the present perspective, the authors outline key therapeutic opportunities and hurdles in clinical sarcoma research, focusing on specific examples of sarcomas that are on the verge of new breakthroughs, as well as those in which promise has not lived up to expectations. Focused clinical trial design, ideally with several biomarker or histology-specific arms, is one means to be simultaneously parsimonious and inclusive. Clin Cancer Res; 18(21); 5837–44. ©2012 AACR.
Drug Resistance to Inhibitors of the Human Double Minute-2 E3 Ligase Is Mediated by Point Mutations of p53, but Can Be Overcome with the p53 Targeting Agent RITA
Authors: Jones Richard J. , Bjorklund Chad C. , Baladandayuthapani Veerabhadran , Kuhn Deborah J. , Orlowski Robert Z. 
Published: August 2012

Abstract
The human double minute (HDM)-2 E3 ubiquitin ligase plays a key role in p53 turnover and has been validated preclinically as a target in multiple myeloma (MM) and mantle cell lymphoma (MCL). HDM-2 inhibitors are entering clinical trials, and we therefore sought to understand potential mechanisms of resistance in lymphoid models. Wild-type p53 H929 MM and Granta-519 MCL cells resistant to MI-63 or Nutlin were generated by exposing them to increasing drug concentrations. MI-63-resistant H929 and Granta-519 cells were resistant to Nutlin, whereas Nutlin-resistant cells displayed cross-resistance to MI-63. These cells also showed cross-resistance to bortezomib, doxorubicin, cisplatin, and melphalan, but remained sensitive to the small molecule inhibitor RITA (reactivation of p53 and induction of tumor cell apoptosis). HDM-2 inhibitor-resistant cells harbored increased p53 levels, but neither genotoxic nor nongenotoxic approaches to activate p53 induced HDM-2 or p21. Resequencing revealed wild-type HDM-2, but mutations were found in the p53 DNA binding and dimerization domains. In resistant cells, RITA induced a G2–M arrest, upregulation of p53 targets HDM-2, PUMA, and NOXA, and PARP cleavage. Combination regimens with RITA and MI-63 resulted in enhanced cell death compared with RITA alone. These findings support the possibility that p53 mutation could be a primary mechanism of acquired resistance to HDM-2 inhibitors in MCL and MM. Furthermore, they suggest that simultaneous restoration of p53 function and HDM-2 inhibition is a rational strategy for clinical translation. Mol Cancer Ther; 11(10); 2243–53. ©2012 AACR.
Evaluating the Therapeutic Potential of a Non-Natural Nucleotide That Inhibits Human Ribonucleotide Reductase
Authors: Ahmad Md. Faiz , Wan Qun , Jha Shalini , Motea Edward , Berdis Anthony , Dealwis Chris 
Published: August 2012

Abstract
Human ribonucleotide reductase (hRR) is the key enzyme involved in de novo dNTP synthesis and thus represents an important therapeutic target against hyperproliferative diseases, most notably cancer. The purpose of this study was to evaluate the ability of non-natural indolyl-2′-deoxynucleoside triphosphates to inhibit the activity of hRR. The structural similarities of these analogues with dATP predicted that they would inhibit hRR activity by binding to its allosteric sites. In silico analysis and in vitro characterization identified one particular analogue designated as 5-nitro-indolyl-2′-deoxyribose triphosphate (5-NITP) that inhibits hRR. 5-NITP binding to hRR was determined by isothermal titration calorimetry. X-ray crystal structure of 5-NITP bound to RR1 was determined. Cell-based studies showed the anti-cancer effects of the corresponding non-natural nucleoside against leukemia cells. 5-NITP binds to hRR with micromolar affinity. Binding does not induce hexamerization of hRR1 like dATP, the native allosteric inhibitor of hRR that binds with high affinity to the A-site. The X-ray crystal structure of Saccharomyces cerevisiae RR1-5-NITP (ScRR1-5-NITP) complex determined to 2.3 Å resolution shows that 5-NITP does not bind to the A-site but rather at the S-site. Regardless, 5-nitro-indolyl-2′-deoxynucleoside (5-NIdR) produces cytostatic and cytotoxic effects against human leukemia cells by altering cell-cycle progression. Our studies provide useful insights toward developing new inhibitors with improved potency and efficacy against hRR. Mol Cancer Ther; 11(10); 2077–86. ©2012 AACR.
Stroke Assessment With Diffusional Kurtosis Imaging
Authors: Hui Edward S. , Fieremans Els , Jensen Jens H. , Tabesh Ali , Feng Wuwei , Bonilha Leonardo , Spampinato Maria V. , Adams Robert , Helpern Joseph A. 
Published: August 2012

Background and Purpose—
Despite being the gold standard technique for stroke assessment, conventional diffusion MRI provides only partial information about tissue microstructure. Diffusional kurtosis imaging is an advanced diffusion MRI method that yields, in addition to conventional diffusion information, the diffusional kurtosis, which may help improve characterization of tissue microstructure. In particular, this additional information permits the description of white matter (WM) in terms of WM-specific diffusion metrics. The goal of this study is to elucidate possible biophysical mechanisms underlying ischemia using these new WM metrics.

Methods—
We performed a retrospective review of clinical and diffusional kurtosis imaging data of 44 patients with acute/subacute ischemic stroke. Patients with a history of brain neoplasm or intracranial hemorrhages were excluded from this study. Region of interest analysis was performed to measure percent change of diffusion metrics in ischemic WM lesions compared with the contralateral hemisphere.

Results—

Kurtosis maps exhibit distinct ischemic lesion heterogeneity that is not apparent on apparent diffusion coefficient maps. Kurtosis metrics also have significantly higher absolute percent change than complementary conventional diffusion metrics. Our WM metrics reveal an increase in axonal density and a larger decrease in the intra-axonal (D
a
) compared with extra-axonal diffusion microenvironment of the ischemic WM lesion.

Conclusions—
The well-known decrease in the apparent diffusion coefficient of WM after ischemia is found to be mainly driven by a significant drop in the intra-axonal diffusion microenvironment. Our results suggest that ischemia preferentially alters intra-axonal environment, consistent with a proposed mechanism of focal enlargement of axons known as axonal swelling or beading.
Hyperintense Vessels on Acute Stroke Fluid-Attenuated Inversion Recovery Imaging
Authors: Cheng Bastian , Ebinger Martin , Kufner Anna , Köhrmann Martin , Wu Ona , Kang Dong-Wha , Liebeskind David , Tourdias Thomas , Singer Oliver C. , Christensen Soren , Warach Steve , Luby Marie , Fiebach Jochen B. , Fiehler Jens , Gerloff Christian , Thomalla Götz ,   on behalf of the Stroke Imaging Repository (STIR) Investigators
Published: August 2012

Background and Purpose—
Hyperintense vessels (HVs) have been observed in fluid-attenuated inversion recovery imaging of patients with acute ischemic stroke and been linked to slow flow in collateral arterial circulation. Given the potential importance of HV, we used a large, multicenter data set of patients with stroke to clarify which clinical and imaging factors play a role in HV.

Methods—

We analyzed data of 516 patients from the previously published PRE-FLAIR study (
PRE
dictive value of
FLAIR
and DWI for the identification of acute ischemic stroke patients ≤3 and ≤4.5 hours of symptom onset—a multicenter study) study. Patients were studied by MRI within 12 hours of symptom onset. HV were defined as hyperintensities in fluid-attenuated inversion recovery corresponding to the typical course of a blood vessel that was not considered the proximal, occluded main artery ipsilateral to the diffusion restriction. Presence of HV was rated by 2 observers and related to clinical and imaging findings.

Results—

Presence of HV was identified in 240 of all 516 patients (47%). Patients with HV showed larger initial ischemic lesion volumes (median, 12.3 versus 4.9mL;
P
<0.001) and a more severe clinical impairment (median National Institutes of Health Stroke Scale 10.5 versus 6;
P
<0.001). In 198 patients with MR angiography, HVs were found in 80% of patients with vessel occlusion and in 17% without vessel occlusion. In a multivariable logistic regression model, vessel occlusion was associated with HV (OR, 21.7%; 95% CI, 9.6–49.9;
P
<0.001). HV detected vessel occlusion with a specificity of 0.86 (95% CI, 0.80–0.90) and sensitivity of 0.76 (95% CI, 0.69–0.83).

Conclusions—
HVs are a common finding associated with proximal arterial occlusions and more severe strokes. HVs predict arterial occlusion with high diagnostic accuracy.
Burden of Risk Alleles for Hypertension Increases Risk of Intracerebral Hemorrhage
Authors: Falcone Guido J. , Biffi Alessandro , Devan William J. , Jagiella Jeremiasz M. , Schmidt Helena , Kissela Brett , Hansen Björn M. , Jimenez-Conde Jordi , Giralt-Steinhauer Eva , Elosua Roberto , Cuadrado-Godia Elisa , Soriano Carolina , Ayres Alison M. , Schwab Kristin , Pera Joanna , Urbanik Andrzej , Rost Natalia S. , Goldstein Joshua N. , Viswanathan Anand , Pichler Alexander , Enzinger Christian , Norrving Bo , Tirschwell David L. , Selim Magdy , Brown Devin L. , Silliman Scott L. , Worrall Bradford B. , Meschia James F. , Kidwell Chelsea S. , Montaner Joan , Fernandez-Cadenas Israel , Delgado Pilar , Broderick Joseph P. , Greenberg Steven M. , Roquer Jaume , Lindgren Arne , Slowik Agnieszka , Schmidt Reinhold , Flaherty Matthew L. , Kleindorfer Dawn O. , Langefeld Carl D. , Woo Daniel , Rosand Jonathan 
Published: August 2012

Background and Purpose—
Genetic variation influences risk of intracerebral hemorrhage (ICH). Hypertension (HTN) is a potent risk factor for ICH and several common genetic variants (single nucleotide polymorphisms [SNPs]) associated with blood pressure levels have been identified. We sought to determine whether the cumulative burden of blood pressure-related SNPs is associated with risk of ICH and pre-ICH diagnosis of HTN.

Methods—
We conducted a prospective multicenter case–control study in 2272 subjects of European ancestry (1025 cases and 1247 control subjects). Thirty-nine SNPs reported to be associated with blood pressure levels were identified from the National Human Genome Research Institute genomewide association study catalog. Single-SNP association analyses were performed for the outcomes ICH and pre-ICH HTN. Subsequently, weighted and unweighted genetic risk scores were constructed using these SNPs and entered as the independent variable in logistic regression models with ICH and pre-ICH HTN as the dependent variables.

Results—

No single SNP was associated with either ICH or pre-ICH HTN. The blood pressure-based unweighted genetic risk score was associated with risk of ICH (OR, 1.11; 95% CI, 1.02–1.21;
P
=0.01) and the subset of ICH in deep regions (OR, 1.18; 95% CI, 1.07–1.30;
P
=0.001), but not with the subset of lobar ICH. The score was associated with a history of HTN among control subjects (OR, 1.17; 95% CI, 1.04–1.31;
P
=0.009) and ICH cases (OR, 1.15; 95% CI, 1.01–1.31;
P
=0.04). Similar results were obtained when using a weighted score.

Conclusion—
Increasing numbers of high blood pressure-related alleles are associated with increased risk of deep ICH as well as with clinically identified HTN.