Miracle-dz/UniFAR-FTUs huggingface dataset:
A pause sequence enriched at translation start sites drives transcription dynamics in vivo

Transcription takes a pause to consider A short sequence in DNA causes RNA polymerase (RNAP) to pause at thousands of previously undocumented locations in the genome. Larson et al. mapped these pause sites at single-nucleotide resolution in vivo in actively growing bacteria. Transcriptional pausing can be critical for the regulation of gene expression, by allowing RNA folding events and in the recruitment of other transcription factors. Science, this issue p. 1042 A short sequence in DNA causes bacterial RNA polymerase to pause at thousands of locations in the genome. Transcription by RNA polymerase (RNAP) is interrupted by pauses that play diverse regulatory roles. Although individual pauses have been studied in vitro, the determinants of pauses in vivo and their distribution throughout the bacterial genome remain unknown. Using nascent transcript sequencing, we identified a 16-nucleotide consensus pause sequence in Escherichia coli that accounts for known regulatory pause sites as well as ~20,000 new in vivo pause sites. In vitro single-molecule and ensemble analyses demonstrate that these pauses result from RNAP–nucleic acid interactions that inhibit next-nucleotide addition. The consensus sequence also leads to pausing by RNAPs from diverse lineages and is enriched at translation start sites in both E. coli and Bacillus subtilis. Our results thus reveal a conserved mechanism unifying known and newly identified pause events.
Review Article: A review of studies of sexual behaviour of school students in sub-Saharan Africa

Aims: This is a review of articles on sexual behaviour of school students in sub-Saharan Africa published between 1987 and 1999. The objective was to describe what is known in this regard and identify gaps in knowledge. Methods: Literature search using electronic databases and a thumb search of relevant journals identified 47 articles reporting sexual behaviours of school-based young persons aged between 14 and 24 years. Results: The fi ndings indicate a relatively low number of articles when one considers the scope of the problems related to adolescent sexual behaviour in the region; high prevalence rates of sexual intercourse; infrequent use of condoms and other contraceptives; and signifi cant proportions of adolescents who have two or more lifetime sexual partners. More data are needed on the extent to which adolescents engage in non-penetrative sexual behaviour and penetrative sex other than heterosexual vaginal intercourse; characteristics of the sexual partners of adolescents; and proximal psychosocial antecedents of sexual behaviour and consistent risk-reduction behaviours. Conclusions: Cultural infl uences on sexual behaviour, the sensitivity of such research in adolescent populations, and the opportunity afforded by school systems for intervention suggest a need for additional exploratory and methodological studies. Placing such information fi rmly within sociocultural contexts in which young people are raised will better inform effective interventions that both delay the onset of sexual intercourse and encourage use of risk reduction strategies.
Bupivacaine-induced cardiac arrhythmias in sheep.

: Controversy persists about the cardiac toxicity of bupivacaine if accidentally administered intravenously during regional anesthesia. Using awake, unanesthetized sheep, we evaluated the cardiac effects of low and high equivalent doses of lidocaine and bupivacaine given intravenously over 10 s. All animals convulsed within 30 s of injections. Although both drugs significantly increased heart rate and systemic and pulmonary arterial blood pressure for up to 10 min, cardiac output was affected variably. The magnitude of hemodynamic changes that each drug produced did not differ significantly from each other at either dose level. However, of the sheep receiving intravenous lidocaine, none developed arrhythmias other than mild sinus tachycardia and minimal ST-T wave changes (which occurred in 25% of the animals). After intravenous bupivacaine injection, all sheep had transient changes on the EKG and/or arrhythmias (e.g., supraventricular tachycardia; atrioventricular condition blocks; ventricular tachycardia; multiform premature ventricular contractions; wide QRS complexes; ST-T wave changes; and in one animal, fatal ventricular fibrillation). Normal sinus rhythm usually returned within 8-10 min. Arterial blood gas and acid-base values stayed within the normal range during the studies, and serum potassium did not change significantly from control. In conclusion, in conscious adult sheep, equivalent doses of lidocaine or bupivacaine produced similar central nervous system (CNS) toxicity when rapidly injected intravenously. In the absence of marked hypoxia, respiratory or metabolic acidosis, hyperkalemia, or hypotension, serious cardiac arrhythmias occurred after bupivacaine but not lidocaine.
Ossification of renal cell carcinoma: a favorable marker

Although foci of calcification in renal cell carcinoma is frequently observed, ossification is extremely rare and may be a marker for favorable prognosis. We report a case of renal cell carcinoma with a focus of ossification; this case was not detected with imaging techniques prior to surgery and diagnosed initially on pathologic examination, unlike other cases. If the radiographic evaluation for ossification is inconclusive but the mass is extremely hard to palpate or difficult to cut, the surgeon should remember the favorable prognosis of such lesions and might consider a limited procedure such as partial nephrectomy while waiting for pathological analysis.
Oceanic mass transport by mesoscale eddies

Spinning up ocean circulation discretely Ocean eddies with diameters of tens to hundreds of kilometers are an important component of water transport on a global scale. Averaged over periods of many years, ocean circulation is regular and coherent enough to have been described as a conveyor belt. However, over shorter time scales, irregular, discrete events cause significant amounts of water movement—termed mesoscale eddies. Zhang et al. combined data from thousands of autonomous observational devices called ARGO floats with satellite data. The mesoscale eddies moved around as much ocean water as wind or deepwater currents. Science, this issue p. 322 Mesoscale eddies transport as much ocean water as is moved by wind and thermohaline circulation. Oceanic transports of heat, salt, fresh water, dissolved CO2, and other tracers regulate global climate change and the distribution of natural marine resources. The time-mean ocean circulation transports fluid as a conveyor belt, but fluid parcels can also be trapped and transported discretely by migrating mesoscale eddies. By combining available satellite altimetry and Argo profiling float data, we showed that the eddy-induced zonal mass transport can reach a total meridionally integrated value of up to 30 to 40 sverdrups (Sv) (1 Sv = 106 cubic meters per second), and it occurs mainly in subtropical regions, where the background flows are weak. This transport is comparable in magnitude to that of the large-scale wind- and thermohaline-driven circulation.
Neuropathic pain and the electrophysiology and pharmacology of nerve injury

Nociceptive pain serves the useful purpose of alerting the body to potential or actual tissue damage. By contrast, neuropathic pain that results from injury or damage to the nervous system persists long after all signs of the original injury have disappeared. Neuropathic pain presents a significant clinical problem as it responds poorly to classical analgesics such as non‐steroidal anti‐inflammatory drugs (NSAIDs) and to opioids; there is also no single, uniformly well‐tolerated drug that is reliably helpful. Treatment currently involves the use of anticonvulsant and/or antidepressant drugs. Electrophysiological experiments on dorsal root ganglion and spinal cord neurons of nerve‐injured experimental animals are yielding new information on the pathophysiology of neuropathic pain. Analysis of actions of various neuropeptides and neurotransmitters in these models has helped to explain the poor efficacy of opioids and suggests new therapeutic approaches to the management of neuropathic pain. Drugs that stimulate α2‐c‐adrenoceptors or that mimic the actions of neuropeptide Y, galanin, or the opioid‐like peptide, nociceptin, may be of use in this regard. Drug Dev. Res. 54:140–153, 2002. © 2002 Wiley‐Liss, Inc.
Successful Treatment of Neonatal Meningitis Caused by Chryseobacterium meningosepticum With Intravenous Ciprofloxacin and Trimethoprim-Sulfamethoxazole

A 5-day-old female infant developed meningitis due to Chryseobacterium meningosepticum. Although the isolate was resistant to empirical antibiotics such as penicillins, cephalosporins, and aminoglycosides, she was successfully treated with intravenous ciprofloxacin and trimethoprim-sulfamethoxazole without adverse reactions including arthropathy and jaundice. This result justifies the use of ciprofloxacin and trimethoprim-sulfamethoxazole for neonatal meningitis caused by C. meningosepticum. (Infect Dis Clin Pract 2008;16:137Y138) Chryseobacterium meningosepticum, formerly known as Flavobacterium meningosepticum, is a gram-negative bacillus, which has been known to cause meningitis in newborns. Neonatal meningitis caused by C. meningosepticum, which is uniformly resistant to commonly used antibiotics, is associated with high mortality rate and severe neurological sequelae. Although a previous report had focused on the efficacy of vancomycin and rifampin, the standard regimen for antimicrobial chemotherapy against C. meningosepticum is still in controversy. Thus, we describe a case of C. meningosepticum meningitis successfully treated with ciprofloxacin and trimethoprim-sulfamethoxazole.
From aerosol-limited to invigoration of warm convective clouds

Invigorating convection in warm clouds Atmospheric aerosols—tiny airborne particles—affect the way clouds form and how they affect climate. Koren et al. investigated how the formation of warm clouds, such as those that form over the oceans, depends on pollution levels (see the Perspective by Remer). Aerosols affect cloud formation in cleaner air disproportionately more than in more polluted air. Before the widespread air pollution of the industrial era, it seems, warm convective clouds may have covered much less of the oceans than they do today. Science, this issue p. 1143; see also p. 1089 Low concentrations of atmospheric aerosols have a dramatic effect on the invigoration of convection in warm clouds. [Also see Perspective by Remer] Among all cloud-aerosol interactions, the invigoration effect is the most elusive. Most of the studies that do suggest this effect link it to deep convective clouds with a warm base and cold top. Here, we provide evidence from observations and numerical modeling of a dramatic aerosol effect on warm clouds. We propose that convective-cloud invigoration by aerosols can be viewed as an extension of the concept of aerosol-limited clouds, where cloud development is limited by the availability of cloud-condensation nuclei. A transition from pristine to slightly polluted atmosphere yields estimated negative forcing of ~15 watts per square meter (cooling), suggesting that a substantial part of this anthropogenic forcing over the oceans occurred at the beginning of the industrial era, when the marine atmosphere experienced such transformation.
Life-span extension by a metacaspase in the yeast Saccharomyces cerevisiae

Yeast metacaspase: Grim Reaper or savior? Yeast metacaspases are structural and possibly functional homologs of caspases that execute apoptosis—programmed cell death—in higher organisms. Malmgren Hill et al. tested whether yeast metacaspase Mca1 acts as an executioner or beneficial protein during replicative aging of yeast (see the Perspective by Kampinga). Boosting metacaspase levels caused a substantial and robust extension of life span. This lifespan extension was only partly dependent on the caspase activity of Mca1 but required the presence of the protein disaggregase Hsp104. Consistent with a role in proteostasis, Mca1 was recruited to chaperone-enriched aggregates during aging. Mca1 increased aggregate asymmetry during yeast cytokinesis and counteracted the age-associated accumulation of inclusions. Science, this issue p. 1389; see also p. 1341 An enzyme linked to cell death in animal cells protects yeast cells from misfolded protein aggregates. [Also see Perspective by Kampinga] Single-cell species harbor ancestral structural homologs of caspase proteases, although the evolutionary benefit of such apoptosis-related proteins in unicellular organisms is unclear. Here, we found that the yeast metacaspase Mca1 is recruited to the insoluble protein deposit (IPOD) and juxtanuclear quality-control compartment (JUNQ) during aging and proteostatic stress. Elevating MCA1 expression counteracted accumulation of unfolded proteins and aggregates and extended life span in a heat shock protein Hsp104 disaggregase– and proteasome-dependent manner. Consistent with a role in protein quality control, genetic interaction analysis revealed that MCA1 buffers against deficiencies in the Hsp40 chaperone YDJ1 in a caspase cysteine–dependent manner. Life-span extension and aggregate management by Mca1 was only partly dependent on its conserved catalytic cysteine, which suggests that Mca1 harbors both caspase-dependent and independent functions related to life-span control.
Tolerance for Predatory Wildlife

Can individual tolerance toward predators affect the success of predator conservation? Around the world, populations of many large, predatory animals are declining, with wide-ranging consequences for other species and ecosystem services (1). The declines have a variety of causes, but for mammalian carnivores and sharks, direct human causes of mortality predominate (2). Scientists and policy-makers have concluded that promoting human tolerance is critical to the success of predator conservation efforts (1, 3–5). Yet the factors that affect people's tolerance of wildlife are not well understood.
Sdo1p, the yeast orthologue of Shwachman–Bodian–Diamond syndrome protein, binds RNA and interacts with nuclear rRNA‐processing factors

The Shwachman–Bodian–Diamond syndrome protein (SBDS) is a member of a highly conserved protein family of not well understood function, with putative orthologues found in different organisms ranging from Archaea, yeast and plants to vertebrate animals. The yeast orthologue of SBDS, Sdo1p, has been previously identified in association with the 60S ribosomal subunit and is proposed to participate in ribosomal recycling. Here we show that Sdo1p interacts with nucleolar rRNA processing factors and ribosomal proteins, indicating that it might bind the pre‐60S complex and remain associated with it during processing and transport to the cytoplasm. Corroborating the protein interaction data, Sdo1p localizes to the nucleus and cytoplasm and co‐immunoprecipitates precursors of 60S and 40S subunits, as well as the mature rRNAs. Sdo1p binds RNA directly, suggesting that it may associate with the ribosomal subunits also through RNA interaction. Copyright © 2009 John Wiley & Sons, Ltd.
A sense of self for Unix processes

A method for anomaly detection is introduced in which "normal" is defined by short-range correlations in a process' system calls. Initial experiments suggest that the definition is stable during normal behaviour for standard UNIX programs. Further; it is able to detect several common intrusions involving sendmail and 1pr. This work is part of a research program aimed at building computer security systems that incorporate the mechanisms and algorithms used by natural immune systems.
New selectable host–marker systems for multiple genetic manipulations based on TRP1, MET2 and ADE2 in the methylotrophic yeast Hansenula polymorpha

Interest has been increasing in the thermotolerant methylotrophic yeast Hansenula polymorpha as a useful system for fundamental research and applied purposes. Only a few genetic marker genes and auxotrophic hosts are yet available for this yeast. Here we isolated and developed H. polymorpha TRP1, MET2 and ADE2 genes as selectable markers for multiple genetic manipulations. The H. polymorpha TRP1 (HpTRP1), MET2 (HpMET2) and ADE2 (HpADE2) genes were sequentially disrupted, using an HpURA3 pop‐out cassette in H. polymorpha to generate a series of new multiple auxotrophic strains, including up to a quintuple auxotrophic strain. Unexpectedly, the HpTRP1 deletion mutants required additional tryptophan supplementation for their full growth, even on complex media such as YPD. Despite the clearly increased resistance to 5‐fluoroanthranilic acid of the HpTRP1 deletion mutants, the HpTRP1 blaster cassette does not appear to be usable as a counter‐selection marker in H. polymorpha. Expression vectors carrying HpADE2, HpTRP1 or HpMET2 with their own promoters and terminators as selectable markers were constructed and used to co‐transform the quintuple auxotrophic strain for the targeted expression of a heterologous gene, Aspergillus saitoi MsdS, at the ER, the Golgi and the cell surface, respectively. The nucleotide sequences presented here were submitted to GenBank under Accession Nos AY795576 (HpTRP1), FJ226453 (HpMET2) and FJ493241 (HpADE2), respectively. Copyright © 2009 John Wiley & Sons, Ltd.
Sunlight controls water column processing of carbon in arctic fresh waters

Illuminating the pathway to destruction Arctic lakes are an important source of atmospheric CO2 and therefore play a role in climate change. It is thus vital to know how the rapid Arctic warming will affect them. Cory et al. now show that light is the biggest culprit in the breakdown of carbon from thawing permafrost soils (see the Perspective by Tranvik). This carbon then moves out into Arctic lakes and streams. Contrary to previous expectations, these photochemical processes cause much more destruction of the organic molecules in fresh water than bacterial respiration does. Science, this issue p. 925; see also p. 870 Photochemical reactions cause most of the breakdown of carbon released from permafrost into arctic inland waters. [Also see Perspective by Tranvik] Carbon in thawing permafrost soils may have global impacts on climate change; however, the factors that control its processing and fate are poorly understood. The dominant fate of dissolved organic carbon (DOC) released from soils to inland waters is either complete oxidation to CO2 or partial oxidation and river export to oceans. Although both processes are most often attributed to bacterial respiration, we found that photochemical oxidation exceeds rates of respiration and accounts for 70 to 95% of total DOC processed in the water column of arctic lakes and rivers. At the basin scale, photochemical processing of DOC is about one-third of the total CO2 released from surface waters and is thus an important component of the arctic carbon budget.
Economic adjustment and current trends in child survival: the case of Zimbabwe

The relationship between health and welfare policies and economic performance and the efficacy of economic adjustment measures in Zimbabwe since independence are examined along with the accompanying changes in infant and young child health. As a result of the successful struggle for independence certain economic measures and social reforms have been instituted and these have had a positive influence on health. The most important include the setting of minimum wages for all categories of labor food subsidies the land resettlement program expanded education water development and drought relief programs. The management and delivery of health care; in line with the new primary health care (PHC) approach has been transformed slowly. The curative and preventive services have been integrated in provincial and district health team structures accountable both to higher levels of the health structure and to the local government structures at the level of service. Active steps have been taken to reform medical education to make the training of physicians more relevant to the needs of Zimbabwe. Some of the changes introduced since independence include: free health care; hospital and rural health center building program; the Zimbabwe expanded program on immunization (ZEPI); diarrheal disease control program (DDCP); a national nutrition program; a program of child spacing; and a national village health worker program. All these and other programs call for expansion of government expenditures. A table shows how the vote allocations and the actual expenditure of the Ministry of Health changed over the period. Due to the scarcity of data it is difficult to be anything but speculative regarding the impact of the health sector interventions on infant and child mortality and morbidity. Yet it is likely that certain programs -- particularly ZEPI and DDCP - have had and continue to have a rapid positive impact on child survival. Any significant impact on deaths resulting from respiratory infections low birth weight and other neonatal causes as well as deaths resulting either directly or indirectly from malnutrition would require improvements in nutritional status of both children and mothers as well as reductions in levels of crowding and further improvement in access to health care. The primary effect on the health sector of the recession period has been to restrict the Ministry of Healths ability to finance services.
Repeated capture of a cytoplasmic linear plasmid by the host nucleus in Debaryomyces hansenii

Debaryomyces hansenii is a halotolerant yeast species that has been shown to carry various nuclear genes of plasmid or viral origin (NUPAVs). However, a recent ancestor of such NUPAVs has not been identified. Here we determined for the first time the molecular structure of an entire cytoplasmic linear plasmid, pDH1A, indigenous to this species. The element is related to non‐autonomous killer plasmids from Kluyveromyces lactis and Pichia acaciae and carries a B‐type DNA polymerase as well as remnants of a killer toxin system, a secreted chitin‐binding protein. Other essential toxin subunits or an immunity function, however, appear to be lost, while two additional small open reading frames are present. Transcripts for all four genes located on pDH1A could be verified by RT–PCR. Interestingly, all genes from pDH1A could be identified as ancestors of NUPAVs located at different chromosomes within the nucleus of D. hansenii, suggesting repeated nuclear capture of fragments originating from pDH1A. The sequence of pDH1A has been deposited in the GenBank data library, Accession No. JN624283. Copyright © 2012 John Wiley & Sons, Ltd.
Limits on Yields in the Corn Belt

Increasing vapor pressure deficit and drought sensitivity will limit future corn yields in the U.S. Midwest. [Also see Report by Lobell et al.] In total global production, corn (maize, Zea mays L.) is the most important food and feed crop. Of the 967 million metric tons produced in 2013, 36.5% were produced in the United States, mostly in the Midwest Corn Belt. The United States is by far the world's largest corn exporter, accounting for 50% of corn exports globally (1, 2). Until recently, breeding and management have allowed farmers to increase the number of plants per acre without loss of yield per plant. On page 516 of this issue, Lobell et al. (3) use a detailed data set for farms across the Corn Belt, to show that increasing yields have been accompanied by rising drought sensitivity, with important implications for future crop yields.