Substantial and sustained reduction in under-5 mortality, diarrhea, and pneumonia in Oshikhandass, Pakistan: evidence from two longitudinal cohort studies 15 years apart.

BACKGROUND: Oshikhandass is a rural village in northern Pakistan where a 1989-1991 verbal autopsy study showed that diarrhea and pneumonia were the top causes of under-5 mortality. Intensive surveillance, active community health education and child health interventions were delivered in 1989-1996; here we assess improvements in under-5 mortality, diarrhea, and pneumonia over this period and 15 years later. METHODS: Two prospective open-cohort studies in Oshikhandass from 1989 to 1996 (Study 1) and 2011-2014 (Study 2) enrolled all children under age 60 months. Study staff trained using WHO guidelines, conducted weekly household surveillance and promoted knowledge on causes and management of diarrhea and pneumonia. Information about household characteristics and socioeconomic status was collected. Hurdle models were constructed to examine putative risk factors for diarrhea and pneumonia. RESULTS: Against a backdrop of considerable change in the socioeconomic status of the community, under-5 mortality, which declined over the course of Study 1 (from 114.3 to 79.5 deaths/1000 live births (LB) between 1989 and 1996), exceeded Sustainable Development Goal 3 by Study 2 (19.8 deaths/ 1000 LB). Reductions in diarrhea prevalence (20.3 to 2.2 days/ Child Year [CY]), incidence (2.1 to 0.5 episodes/ CY), and number of bloody diarrhea episodes (18.6 to 5.2%) seen during Study 1, were sustained in Study 2. Pneumonia incidence was 0.5 episodes /CY in Study 1 and 0.2/CY in Study 2; only 5% of episodes were categorized as severe or very severe in both studies. While no individual factors predicted a statistically significant difference in diarrhea or pneumonia episodes, the combined effect of water, toilet and housing materials was associated with a significant decrease in diarrhea; higher household income was the most protective factor for pneumonia in Study 1. CONCLUSIONS: We report a 4-fold decrease in overall childhood mortality, and a 2-fold decrease in childhood morbidity from diarrhea and pneumonia in a remote rural village in Pakistan between 1989 and 2014. We conclude that significant, sustainable improvements in child health may be achieved through improved socioeconomic status and promoting interactions between locally engaged health workers and the community, but that continued efforts are needed to improve health worker training, supervision, and the rational use of medications. TRIAL REGISTRATION: Not Applicable.

Short communication: Identifying challenges and opportunities for improved nutrient management through the USDA's Dairy Agroecosystem Working Group.

Nutrient management on US dairy farms must balance an array of priorities, some of which conflict. To illustrate nutrient management challenges and opportunities across the US dairy industry, the USDA Agricultural Research Service Dairy Agroecosystems Working Group (DAWG) modeled 8 confinement and 2 grazing operations in the 7 largest US dairy-producing states using the Integrated Farm System Model (IFSM). Opportunities existed across all of the dairies studied to increase on-farm feed production and lower purchased feed bills, most notably on large dairies (>1,000 cows) with the highest herd densities. Purchased feed accounted for 18 to 44% of large dairies' total operating costs compared with 7 to 14% on small dairies (<300 milk cows) due to lower stocking rates. For dairies with larger land bases, in addition to a reduction in environmental impact, financial incentives exist to promote prudent nutrient management practices by substituting manure nutrients or legume nutrients for purchased fertilizers. Environmental priorities varied regionally and were principally tied to facility management for dry-lot dairies of the semi-arid western United States (ammonia-N emissions), to manure handling and application for humid midwestern and eastern US dairies (nitrate-N leaching and P runoff), and pasture management for dairies with significant grazing components (nitrous oxide emissions). Many of the nutrient management challenges identified by DAWG are beyond slight modifications in management and require coordinated solutions to ensure an environmentally and economically sustainable US dairy industry.

Advancing the Sustainability of US Agriculture through Long-Term Research.

Agriculture in the United States must respond to escalating demands for productivity and efficiency, as well as pressures to improve its stewardship of natural resources. Growing global population and changing diets, combined with a greater societal awareness of agriculture's role in delivering ecosystem services beyond food, feed, fiber, and energy production, require a comprehensive perspective on where and how US agriculture can be sustainably intensified, that is, made more productive without exacerbating local and off-site environmental concerns. The USDA's Long-Term Agroecosystem Research (LTAR) network is composed of 18 locations distributed across the contiguous United States working together to integrate national and local agricultural priorities and advance the sustainable intensification of US agriculture. We explore here the concept of sustainable intensification as a framework for defining strategies to enhance production, environmental, and rural prosperity outcomes from agricultural systems. We also elucidate the diversity of factors that have shaped the past and present conditions of cropland, rangeland, and pastureland agroecosystems represented by the LTAR network and identify priorities for research in the areas of production, resource conservation and environmental quality, and rural prosperity. Ultimately, integrated long-term research on sustainable intensification at the national scale is critical to developing practices and programs that can anticipate and address challenges before they become crises.

Endurance exercise training promotes medullary hematopoiesis.

Endurance exercise is a poorly defined yet powerful mediator of hematopoiesis. The purpose of this study was to directly investigate the effects of endurance exercise training on hematopoiesis and to identify potential mechanisms responsible for any observed changes. Four-week-old male C57Bl/6 mice were trained on a treadmill at progressive speeds over a 10-wk period. Tissues were harvested 2 d following the final training session. Flow cytometry, the cobblestone area-forming cell assay, and the methycellulose colony-forming unit assay were used to assess medullary and mobilized hematopoietic stem and progenitor cells. Quantitative real-time PCR and Western blots were used to measure hematopoietic cytokine production. Histochemistry was also used to assess adaptations to exercise in the bone marrow niche. Depending on the cell type, endurance training increased medullary and mobilized hematopoietic stem and progenitor cell content from 50 to 800%. Training also reduced marrow cavity fat by 78%. Skeletal muscle hematopoietic cytokine expression was also increased at least 60% by training. Sedentary mice served as controls for the above experiments. In conclusion, endurance exercise training greatly promotes hematopoiesis and does so through improvements in medullary niche architecture as well as increased skeletal muscle hematopoietic cytokine production.

The role of booster vaccination and ongoing viral evolution in seasonal circulation of SARS-CoV-2.

Periodic resurgences of COVID-19 in the coming years can be expected, while public health interventions may be able to reduce their intensity. We used a transmission model to assess how the use of booster doses and non-pharmaceutical interventions (NPIs) amid ongoing pathogen evolution might influence future transmission waves. We find that incidence is likely to increase as NPIs relax, with a second seasonally driven surge expected in autumn 2022. However, booster doses can greatly reduce the intensity of both waves and reduce cumulative deaths by 20% between 7 January 2022 and 7 January 2023. Reintroducing NPIs during the autumn as incidence begins to increase again could also be impactful. Combining boosters and NPIs results in a 30% decrease in cumulative deaths, with potential for greater impacts if variant-adapted boosters are used. Reintroducing these NPIs in autumn 2022 as transmission rates increase provides similar benefits to sustaining NPIs indefinitely (307 000 deaths with indefinite NPIs and boosters compared with 304 000 deaths with transient NPIs and boosters). If novel variants with increased transmissibility or immune escape emerge, deaths will be higher, but vaccination and NPIs are expected to remain effective tools to decrease both cumulative and peak health system burden, providing proportionally similar relative impacts.

Predicting the long-term impact of rotavirus vaccination in 112 countries from 2006 to 2034: A transmission modeling analysis.

Rotavirus vaccination has been shown to reduce rotavirus burden in many countries, but the long-term magnitude of vaccine impacts is unclear, particularly in low-income countries. We use a transmission model to estimate the long-term impact of rotavirus vaccination on deaths and disability adjusted life years (DALYs) from 2006 to 2034 for 112 low- and middle-income countries. We also explore the predicted effectiveness of a one- vs two- dose series and the relative contribution of direct vs indirect effects to overall impacts. To validate the model, we compare predicted percent reductions in severe rotavirus cases with the percent reduction in rotavirus positivity among gastroenteritis hospital admissions for 10 countries with pre- and post-vaccine introduction data. We estimate that vaccination would reduce deaths from rotavirus by 49.1 % (95 % UI: 46.6-54.3 %) by 2034 under realistic coverage scenarios, compared to a scenario without vaccination. Most of this benefit is due to direct benefit to vaccinated individuals (explaining 69-97 % of the overall impact), but indirect protection also appears to enhance impacts. We find that a one-dose schedule would only be about 57 % as effective as a two-dose schedule 12 years after vaccine introduction. Our model closely reproduced observed reductions in rotavirus positivity in the first few years after vaccine introduction in select countries. Rotavirus vaccination is likely to have a substantial impact on rotavirus gastroenteritis and its mortality burden. To sustain this benefit, the complete series of doses is needed.

Functional neuroanatomy of interoceptive processing in children and adolescents: a pilot study.

In adults, interoception - the sense of the physiological condition of the body - appears to influence emotion processing, cognition, behavior and various somatic and mental health disorders. Adults demonstrate frontal-insula-parietal-anterior cingulate cortex activation during the heartbeat detection task, a common interoceptive measure. Little, however, is known about the functional neuroanatomy underlying interoception in children. The current pilot study examined interoceptive processing in children and adolescents with fMRI while using the heartbeat detection task. Our main findings demonstrate that children as young as the age of six activate the left insula, cuneus, inferior parietal lobule and prefrontal regions. These findings are similar to those in adults when comparing heartbeat and tone detection conditions. Age was associated with increased activation within the dACC, orbital frontal cortex and the mid-inferior frontal gyri. Thus, our pilot study may provide important information about the neurodevelopment of interoceptive processing abilities in children and a task for future interoception neuroimaging studies in children.

Use of quaternized cassia galactomannan for hair conditioning.

There is a continuing need for hair care formulas to deliver superior conditioning benefits with highly efficient deposition of hair-enhancing components. In this paper, we describe high-charge-density (3.0 mEq/g) cassia hydroxypropyltrimonium chloride (cassia HPTC), a quaternized galactomannan from the endosperm of Cassia tora and Cassia obtusifolia. Cassia HPTC is shown to participate in the coacervate phase of conditioning shampoos, from which it is deposited onto hair to provide conditioning benefits. Cryo-scanning electron microscopy and time-of-flight secondary ion mass spectrometry were used to observe and characterize the cassia HPTC deposits left on hair. The high-charge-density cassia HPTC resulted in improved deposition efficiency compared with a quaternized guar-containing formula. Cassia HPTC offers benefits as an alternative to traditional cationic polymers as conditioning agents or as an adjunct conditioner to decrease the amount of cationic polymer needed to achieve the desired conditioning performance.

A geostatistical approach to identify and mitigate agricultural nitrous oxide emission hotspots.

Anthropogenic emissions of nitrous oxide (N2O), a trace gas with severe environmental costs, are greatest from agricultural soils amended with nitrogen (N) fertilizer. However, accurate N2O emission estimates at fine spatial scales are made difficult by their high variability, which represents a critical challenge for the management of N2O emissions. Here, static chamber measurements (n=60) and soil samples (n=129) were collected at approximately weekly intervals (n=6) for 42-d immediately following the application of N in a southern Minnesota cornfield (15.6-ha), typical of the systems prevalent throughout the U.S. Corn Belt. These data were integrated into a geostatistical model that resolved N2O emissions at a high spatial resolution (1-m). Field-scale N2O emissions exhibited a high degree of spatial variability, and were partitioned into three classes of emission strength: hotspots, intermediate, and coldspots. Rates of emission from hotspots were 2-fold greater than non-hotspot locations. Consequently, 36% of the field-scale emissions could be attributed to hotspots, despite representing only 21% of the total field area. Variations in elevation caused hotspots to develop in predictable locations, which were prone to nutrient and moisture accumulation caused by terrain focusing. Because these features are relatively static, our data and analyses indicate that targeted management of hotspots could efficiently reduce field-scale emissions by as much 17%, a significant benefit considering the deleterious effects of atmospheric N2O.

The use of colposcopy in assessing vaginal irritation in research.

Since the early 1990s, colposcopy of the vagina and cervix has been used in the development of vaginal products in order to detect epithelial changes that may increase the likelihood of HIV or acquisition of other sexually transmitted diseases. As part of a continued effort to examine and define the role of colposcopy in a research setting, the Contraceptive Research and Development Program (CONRAD) and the International Working Group on Microbicides (IWGM), in association with the United Nations Program for AIDS (UNAIDS) sponsored a conference entitled, 'The Use of Colposcopy in Assessing Vaginal Irritation in Research', held in Washington, DC in January 1999. This is a report of that conference. The World Health Organization's colposcopy procedure and nomenclature, published in 1995, were reviewed and changes were recommended. The revised procedure involves colposcopic examination of the external genitalia, naked eye examination of the cervix, fornices, and vaginal walls, followed by lavage and colposcopic examination of those areas, and sampling as appropriate for microscopic examination. Revised nomenclature replaces the terms used for findings with descriptions of what is actually seen. Digital video imaging and testing for inflammatory markers may be adjuncts to colposcopy and should be further studied. Other areas requiring additional research include the natural history of colposcopic changes, factors other than product use that may affect colposcopic findings, the clinical significance of findings, and the procedure which best assesses these findings.

Effects of long-term treatment with contraceptive steroids on plasma and brain tryptophan, brain 5-hydroxytryptamine, and locomotor activity in female mice [proceedings].

PIP: The effects of prolonged daily injections of norethistrone acetate (200 mcg/kg) alone and in combination with ethinyl estradiol (100 mcg/kg) were compared with daily vehicle injection. Locomotor activity was determined continuously for 2 estrus cycles prior to injection, the every 7th day throughout 42 days of treatment. Free and total plasma tryptophan and brain tryptophan and 5-HT (serotonin) were determined on the 43rd day and compared with diestrous values. Locomotor activity declined after both treatments. The norethistrone group had 47% of activity. The combination group was 54% of initial diestrus values. Vehicle controls resumed cyclic changes in locomotor activity within 8 days, while the hormone treatments abolished these cyclic changes. Norethistrone was ineffective in changing brain tryptophan values. The combined treatment caused the reduction of plasma total and free tryptophan, probably due to acceleration of protein synthesis.^ieng

Recovery of sheep hearts after perfusion preservation or static storage with crystalloid media.

BACKGROUND: These experiments were designed to evaluate the viability of large hearts after preservation by use of procedures that have shown good results with small animal hearts. Efficacy of novel long-term preservation protocols should be documented with a large animal model before such procedures can be adopted for clinical use. We studied the recovery of sheep hearts that were perfusion-preserved in media containing two different substrate mixtures and hearts stored without perfusion either in University of Wisconsin solution modified to maintain tissue adenosine triphosphate content or in Stanford solution. METHODS: Six groups of sheep hearts were studied: I, fresh nonpreserved controls; II, hearts perfusion-preserved at 11 degrees C for 24 hours by use of an oxygenated extracellular-type medium with pyruvate + glucose substrate; III, hearts preserved as for II but with aspartate + glutamate + glucose substrate; IV, hearts stored without perfusion at 3 degrees C for 24 hours in University of Wisconsin solution containing 2,3-butanedione monoxime 30 mmol/L, CaCl2 1 mmol/L, and fresh reduced glutathione 3 mmol/L; V, hearts stored without perfusion at 3 degrees C for 4 hours in Stanford solution; VI, hearts preserved as for II but without perfusion. Recovery was measured for 6 hours in a Langendorff model, perfused with an erythrocyte + albumin medium. RESULTS: Hearts that were perfusion-preserved with both substrate mixtures and hearts stored in modified University of Wisconsin solution recovered function that was not significantly different from control subjects. Hearts stored in Stanford medium did not recover as well as did groups II, III, and IV. Left ventricular pressure and peak rate of left ventricular relaxation of the Stanford group were lower, and left ventricular enddiastolic pressure was higher, than those values for controls (repeated measures analysis of variance; Dunnett's procedure). The group VI hearts did not recover function at all. CONCLUSION: The results suggest that large hearts preserved with medium containing either aspartate + glutamate + glucose or pyruvate + glucose have comparable recovery after long-term perfusion preservation. Aspartate + glutamate may offer advantages for clinical use because of their lower production of lactate and better chemical stability compared with pyruvate. Static storage in modified University of Wisconsin solution also produced viable hearts with recovery comparable to perfusion-preserved aspartate + glutamate + glucose hearts. Tests of these preservation media and procedures with large transplanted hearts are warranted.

Steroid pretreatment improves graft recovery in a sheep orthotopic heart transplantation model.

BACKGROUND: Previous reports provide conflicting evidence concerning effects of steroids on recovery of cardiac function during procedures involving cardiopulmonary bypass. This study was designed to test the hypothesis that pretreatment of animals with steroids before heart transplantation improves graft hemodynamic function. METHODS: Four groups of sheep were studied: CON, nonsteroid-treated nontransplanted controls (n = 8); CON-S, steroid-treated nontransplanted controls (n = 5); TX, nonsteroid-treated transplanted animals (n = 5); and TX-S, steroid-treated transplanted animals (n = 5). Steroid-treated animals were given methylprednisolone 30 mg/kg immediately before surgery. Procedures for harvest and orthotopic transplantation were similar to those used clinically. Contractile function, left ventricular diameter, and cardiac output of control and transplanted hearts were measured for 6 hours. A 2 x 2 factorial repeated measures analysis of variance was used to determine statistical significance (p < 0.05). RESULTS: Steroid pretreatment produced significantly higher function in controls and transplanted animals compared with nonsteroid-treated animals. On average over 6 hours, significant steroid effects were observed for left ventricular peak systolic pressure, mm Hg (CON, 85 +/- 2; CON-S, 98 +/- 3; TX, 74 +/- 3; TX-S, 91 +/- 2); global stroke work, mJoule x cm(-2) (CON, 4.69 +/- 0.21; CON-S, 5.88 +/- 0.32; TX, 2.27 +/- 0.17; TX-S, 4.23 +/- 0.16); and peak rate of pressure relaxation (-dP/dt(max)), mm Hg/msec (CON, 1.23 +/- 0.05; CON-S, 1.44 +/- 0.08; TX, 0.60 +/- 0.03; TX-S, 2.04 +/- 0.13). Steroid pretreatment produced more stable recovery for transplanted animals. All five TX-S animals could be removed from inotropic support and had stable function for 6 hours. In contrast, 1 of 5 TX animals could not be removed from inotropic support, and 1 of 5 TX hearts failed 3 hours after transplant. Arterial blood PO2 values were significantly higher in steroid-treated animals than in nonsteroid treated animals. Blood systemic lactate, which was elevated after transplantation, returned to control level by 6 hours in the steroid-treated group but not in the nonsteroid-treated group. CONCLUSION: Steroid pretreatment of heart donors and recipients improved systolic and diastolic function and hemodynamic stability after transplantation. In addition, steroid pretreatment improved pulmonary gas exchange of control and transplanted animals.

Crigler-Najjar disease in pregnancy.

BACKGROUND: Crigler-Najjar disease, a rare cause of maternal unconjugated hyperbilirubinemia in pregnancy, poses no threat to the mother, and the elevated bilirubin levels do not seem harmful to the fetus. However, the disease is expressed in two forms, one of which is fatal. CASE: The maternal total bilirubin (mostly unconjugated) was 8.5 mg/dL in the first trimester, fell to 5.0 mg/dL in the second, and rose again to 8.8 mg/dL at term. The infant was jaundiced at birth, with umbilical cord total bilirubin at 7.6 mg/dL. The jaundice resolved without treatment, and no sequelae of hyperbilirubinemia were present. CONCLUSION: Crigler-Najjar disease type II seems to pose no unique maternal risk during pregnancy. The fetus seems to be resistant to elevated maternal unconjugated bilirubin, but the neonate may required therapy for hyperbilirubinemia.

Detection of primary colorectal cancer with indium 111 monoclonal antibody B72.3.

B72.3 is a murine monoclonal antibody of the immunoglobulin subclass IgG1 directed against TAG-72, a cell surface antigen present on colorectal carcinoma cells. We investigated the utility of scanning with indium 111-labeled B72.3 in 16 patients with a high clinical suspicion of or biopsy-proven primary colorectal cancer. Each patient received 1 or 2 mg of B72.3 monoclonal antibody labeled with 152 MBq of indium 111. Patients underwent scanning 2 to 3 days and 7 days after infusion by planar and emission computed tomography. Nineteen lesions were confirmed in 12 patients. Three patients with benign polyps had true-negative monoclonal antibody scans. Indium 111-labeled imaging of B72.3 detected nine of 19 lesions. Unsuspected tumor sites were identified by monoclonal antibody scan in three patients. By detection of additional abdominal disease and extra-abdominal spread, indium 111-labeled scanning of B72.3 directly affected treatment in 18% of patients.

Use of cardiopulmonary bypass to salvage patients with multiple-chamber heart wounds.

BACKGROUND: The need for cardiopulmonary bypass in the treatment of penetrating heart injuries is debated. OBJECTIVES: To review our experience with penetrating heart injuries and determine the indications and outcome for cardiopulmonary bypass. DESIGN: Retrospective review. SETTING: A university-based, level I trauma center. PATIENTS: All victims of penetrating heart injury presenting between July 1, 1989, and December 31, 1995. METHODS: Medical records were reviewed for demographic and physiological data, operative findings, and outcome. RESULTS: Overall survival for 106 patients with penetrating heart injury was 55%. In an effort to resuscitate the heart, 4 patients with unresponsive cardiogenic shock were placed on cardiopulmonary bypass; none survived. Of 30 patients with multiple-chamber injuries, 11 presented with signs of life and 7 survived. Cardiopulmonary bypass was essential to repair complex injuries in 2 of the 7 survivors. CONCLUSION: Cardiopulmonary bypass was ineffective in salvaging patients with cardiogenic shock but was essential in some patients with complex multiple-chamber cardiac injuries that could not be exposed and repaired by other means.

Early clinical studies with cis-diammine-1,1-cyclobutane dicarboxylate platinum II.

cis-Diammine-1,1-cyclobutane dicarboxylate platinum II (CBDCA, JM8), an analogue of cisplatin showing reduced toxicity in preclinical studies, was evaluated in 60 patients. Doses were given initially every 3 weeks and escalated from 20 to 520 mg/m2. Following this, doses were given every 4 weeks and escalated from 300 to 500 mg/m2. The dose-limiting toxicity, thrombocytopoenia, occurred in four-fifths of patients treated at 520 mg/m2, with the nadir occurring 3 weeks after treatment. Leucopoenia and anaemia also occurred but were less severe. Vomiting occurred in all patients receiving over 120 mg/m2 but seldom persisted beyond 24 h. Serial measurements of 51Cr-EDTA clearances, urinary N-acetylglucosaminidase, urinary leucine aminopeptidase, and beta 2-microglobulin did not reveal significant evidence of nephrotoxicity. Detriment to the audiogram has not been seen in the first 13 patients studied. Pharmacological studies showed that most of the dose of platinum was excreted in the urine, and that impairment of renal function may be associated with drug retention and an increased risk of myelosuppression. The previous therapy and age of the patient also affected the tolerance of the drug. Clinical responses were seen in patients with ovarian carcinoma receiving greater than 120 mg/m2. A further dose escalation was performed on a 4-week schedule in patients under 65 with good renal function. The maximum dose it was possible to administer repeatedly without incurring myelosuppression was in the range 400-500 mg/m2. JM8 is not significantly nephrotoxic and is less emetic than cisplatin. It has antitumour activity in man and deserves wider evaluation, along with the other analogues under study in various centres, as an alternative to cisplatin.

Ethanol kinetics during pregnancy. Study in ewes and their fetuses.

1. Kinetics of placental transfer and elimination of ethanol in maternal and fetal blood and amniotic fluid were studied after iv infusion of ethanol in 3 ewes in the third trimester of pregnancy. 2. Ethanol was transferred rapidly from the maternal to the fetal compartment, and more slowly from these to the amniotic fluid. 3. The kinetics of ethanol elimination from the maternal and fetal circulations were similar, indicating rapid bidirectional transfer between them and elimination from the former only. 4. There was significantly slower elimination of ethanol from the amniotic fluid, with increasing concentrations long after these had started to decline in the maternal and fetal blood. This suggests that the amniotic fluid can act as a reservoir for ethanol storage.

Assay of cytotoxicity and mutagenicity of alkylating agents by using Neurospora spheroplasts.

A system relying on the use of Neurospora crassa spheroplasts has been developed for the assay of cytotoxicity and mutagenicity of chemical compounds. Mutagenicity was assayed by using reversion of alleles in the am gene selected to recognize certain specified transitions and also undefined point mutations. Cytotoxicity was quantified by measuring a 'cytotoxicity parameter', m, which appears in the exponential function that fits the survival/dose curve for each compound (under standard incubation conditions). Of the compounds tested, nitrogen mustard (Cl(CH2)2 NMe(CH2)2Cl) was cytotoxic and non-mutagenic, and ethyl nitrosourea was highly mutagenic but not cytotoxic. Of the remaining compounds tested, methyl nitrosourea, butadiene diepoxide, and cis platin (cis diammonia platinum II chloride) all showed comparable mutagenicity per survivor, although the values of m covered a wide range. Differences were found between the different compounds in the effects of the uvs-2 allele on survival and on the preponderance of G to A transitions.

DNA-DNA and DNA-protein crosslinking and repair in Neurospora crassa following exposure to nitrogen mustard.

A new method was developed for the analysis of DNA-protein crosslinks in Neurospora crassa. The formations of DNA-protein and DNA-DNA crosslinks were assayed following exposure of spheroplasts to HN2. Both types of crosslink were detected and were found to be repaired during recovery. Moreover a mutant sensitive to HN2 was defective in the removal of both types of crosslink.