Development of mucociliary transport in the postnatal ferret trachea.

Little is known of the developmental aspects of mucociliary transport. Previous studies have documented that newborn ferret trachea has very few ciliated cells but numerous immature secretory cells in the epithelium and only rudimentary submucosal glands. Rapid and complete maturation occurs in the first postnatal month. This study examines mucociliary transport during this period of rapid maturation. We made direct observations of particle movement across the epithelium of ferret tracheas. No mucus transport could be demonstrated on the first day of life. Transport was discernible, although sporadic and slow, by 7 days and reached adult levels (10.7 +/- 3.7 mm/min) by 28 postnatal days. The emergence of transport capability correlated well with previously described developmental changes in ciliation, mucus secretion, and ion permeability and transport. Threshold mucus transport occurred at 1 wk of age when 20-25% of the surface cells are ciliated. The neonatal ferret appears to be a useful model for assessing integrated epithelial structure-function relationships that are important not only during early development but also during repair after airway injury involving deciliation.     

The genetic defect in multiple endocrine neoplasia type 2A maps next to the centromere of chromosome 10

Multiple endocrine neoplasia type 2A (MEN2A) is a rare cancer syndrome that is inherited in an apparently autosomal dominant fashion. Previous linkage studies had assigned the MEN2A locus to chromosome 10 in the pericentromeric region. We recently have described several new easily scorable RFLPs for the chromosome 10-specific alpha satellite DNA (the D10Z1) locus that is known, on the basis of previous in situ hybridization experiments, to lie at the centromere. We report here tight linkage between MEN2A and D10Z1, as demonstrated by a maximum lod score of 12.02 at the recombination frequency of zero (1-lod-unit support interval 0-4 cM), indicating that the genetic defect in MEN2A lies in the immediate vicinity of the centromere. By means of a set of ordered polymorphic DNA markers from the pericentromeric region, multipoint as well as pairwise linkage analyses place the MEN2A locus at the middle of a small region (approximately 11 cM) bracketing the centromere with FNRB (at 10p11.2) and RBP3 (at 10q11.2) on either side, providing further support for the centromeric location of the MEN2A locus. Marked sex difference in recombination frequencies exists in this pericentromeric region: significantly (P less than .01) more female than male crossovers were observed across all of the adjacent intervals D10S24-FNRB, FNRB-D10Z1, and D10Z1-RBP3. However, a sex difference was not seen in the 7-cM interval from RBP3 to D10S5, suggesting that large variation in the sex difference in recombination can occur over small chromosomal regions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunocytochemical demonstration of nerve growth factor and histofluorescence of catecholaminergic nerves in the salivary glands of diabetic mice

Summary Nerve growth factor (NGF) was localized in the submandibular, sublingual, and parotid salivary glands of male and female diabetic mice and their normal littermates by immunoperoxidase staining usingp-phenylenediamine-pyrocatechol as a chromogen for the cytochemical demonstration of peroxidase activity. In the normal male submandibular gland, immunoreactive NGF was localized in the apical regions of granular, intercalated and collecting duct cells, while in the normal female submandibular gland, NGF was present throughout the cytoplasm of granular duct cells. The localization of NGF in the diabetic male and female submandibular glands was similar and resembled that of the normal female. NGF immunoreactivity was also observed in the striated duct cells in the sublingual and parotid glands of all four types of mice.The sympathetic innervation of the submandibular glands of normal and diabetic mice was demonstrated using glyoxylic acid-induced histofluorescence. The pattern of sympathetic innervation and the intensity of catecholamine fluorescence was consistently different in the four types of mice. In the normal male submandibular gland the fluorescence was very intense, particularly in nerves adjacent to the granular ducts. In the normal female submandibular gland, the fluorescence was weak, while in the diabetic male and female the fluorescence was moderate.The correlation between the intensity of the immunocytochemical staining for NGF and the catecholamine fluorescence adjacent to the granular ducts suggests a trophic influence of the NGF-containing granular ducts on their sympathetic innervation.     

Selective killing of Leishmania infected mouse macrophages by 6-methylpurine 2′-deoxyriboside

6-methylpurine 2′-deoxyriboside killed mouse macrophages infected with amastigotes of $\text{Leishmania donovani}$ and $\text{Leishmania mexicana}$, but did not affect the growth of non-parasitized cells. $\text{Leishmania}$ extracts cleaved the non-toxic 6-methylpurine 2′-deoxyriboside to 6-methylpurine, a potent adenine antimetabolite for mammalian cells. By eliminating macrophages latently infected with $\text{Leishmania donovani}$ amastigotes, 6-methylpurine 2′-deoxyriboside could augment the effects of leishmanicidal agents $\text{in vivo}$.     

Growth characteristics of atypical mycobacteria in water and their comparative resistance to disinfectants.

With the increasing significance of group IV atypical mycobacteria as etiological agents in a variety of infections, studies were conducted to determine their growth capabilities in water and their comparative resistance to disinfectants used to decontaminate hospital equipment. Isolates of Mycobaterium chelonei (TM strains) from peritoneal fluids of patients and peritoneal dialysis machines were able to multiply in commercial distilled water, with generation times at 25 degrees C ranging from 8 to 15 h. Levels of 10(5) to 10(6) cells per ml were attained, and these stationary-phase populations declined only slightly over a 1-year period. Results of studies to determine resistance to disinfectants showed the following. (i) TM strains of M. chelonei cultured in commercial distilled water showed survivors in 2% aqueous formaldehyde (HCHO) solutions up to 24 h; in 8% HCHO, only a 2-log reduction in viable counts was observed over a 2-h sampling period. Reference ATCC strains of M. chelonei and M. fortuitum were rapidly inactivated, with no survivors after 2 h of exposure to 2% HCHO or 15 min of exposure to 8% HCHO. (ii) In 2% alkaline glutaraldehyde, TM strains survived 60 min. whereas ATCC strains showed no survivors after 2 min of contact time. (iii) All M. chelonei and M. fortuitum strains survived 60 min of exposure to concentrations of 0.3 and 0.7 microgram of free chlorine per ml at pH 7.     

Simple radio-immunoassay for the measurement of human and rat IgE levels by ammonium sulfate precipitation.

A simple assay for quantitating IgE levels has been developed based on the observation that antibody-bound IgE is insoluble in 33 percent saturated (NH-4)2-SO-4 whereas unbound IgE is not. The method has been applied to human and rat IgE. Some preliminary results on IgE levels in parasite-injected rats are presented.     

Sex differences in the immune response to acute COVID-19 respiratory tract infection

Determine if sex differences exist in clinical characteristics and outcomes of adults hospitalized for coronavirus disease 2019 (COVID-19) in a US healthcare system. Case series study. Sequentially hospitalized adults admitted for COVID-19 at two tertiary care academic hospitals in New Orleans, LA, between 27 February and 15 July 2020. Measures included demographics, comorbidities, presenting symptoms, and laboratory results. Outcomes included intensive care unit admission (ICU), invasive mechanical ventilation (IMV), and in-hospital death. We included 776 patients (median age 60.5 years; 61.4% women, 75% non-Hispanic Black). Rates of ICU, IMV, and death were similar in both sexes. In women versus men, obesity (63.8 vs 41.6%, P < 0.0001), hypertension (77.6 vs 70.1%, P = 0.02), diabetes (38.2 vs 31.8%, P = 0.06), chronic obstructive pulmonary disease (COPD, 22.1 vs 15.1%, P = 0.015), and asthma (14.3 vs 6.9%, P = 0.001) were more prevalent. More women exhibited dyspnea (61.2 vs 53.7%, P = 0.04), fatigue (35.7 vs 28.5%, P = 0.03), and digestive symptoms (39.3 vs 32.8%, P = 0.06) than men. Obesity was associated with IMV at a lower BMI (> 35) in women, but the magnitude of the effect of morbid obesity (BMI ≥ 40) was similar in both sexes. COPD was associated with ICU (adjusted OR (aOR), 2.6; 95%CI, 1.5–4.3) and IMV (aOR, 1.8; 95%CI, 1.2–3.1) in women only. Diabetes (aOR, 2.6; 95%CI, 1.2–2.9), chronic kidney disease (aOR, 2.2; 95%CI, 1.3–5.2), elevated neutrophil-to-lymphocyte ratio (aOR, 2.5; 95%CI, 1.4–4.3), and elevated ferritin (aOR, 3.6; 95%CI, 1.7–7.3) were independent predictors of death in women only. In contrast, elevated D-dimer was an independent predictor of ICU (aOR, 7.3; 95%CI, 2.7–19.5), IMV (aOR, 6.5; 95%CI, 2.1–20.4), and death (aOR, 4.5; 95%CI, 1.2–16.4) in men only. This study highlights sex disparities in clinical determinants of severe outcomes in COVID-19 patients that may inform management and prevention strategies to ensure gender equity.     

Multi-organ Abnormalities and mTORC1 Activation in Zebrafish Model of Multiple Acyl-CoA Dehydrogenase Deficiency

Multiple Acyl-CoA Dehydrogenase Deficiency (MADD) is a severe mitochondrial disorder featuring multi-organ dysfunction. Mutations in either the ETFA, ETFB, and ETFDH genes can cause MADD but very little is known about disease specific mechanisms due to a paucity of animal models. We report a novel zebrafish mutant dark xavier (dxa^vu463) that has an inactivating mutation in the etfa gene. dxa^vu463 recapitulates numerous pathological and biochemical features seen in patients with MADD including brain, liver, and kidney disease. Similar to children with MADD, homozygote mutant dxa^vu463 zebrafish have a spectrum of phenotypes ranging from moderate to severe. Interestingly, excessive maternal feeding significantly exacerbated the phenotype. Homozygous mutant dxa^vu463 zebrafish have swollen and hyperplastic neural progenitor cells, hepatocytes and kidney tubule cells as well as elevations in triacylglycerol, cerebroside sulfate and cholesterol levels. Their mitochondria were also greatly enlarged, lacked normal cristae, and were dysfunctional. We also found increased signaling of the mechanistic target of rapamycin complex 1 (mTORC1) with enlarged cell size and proliferation. Treatment with rapamycin partially reversed these abnormalities. Our results indicate that etfa gene function is remarkably conserved in zebrafish as compared to humans with highly similar pathological, biochemical abnormalities to those reported in children with MADD. Altered mTORC1 signaling and maternal nutritional status may play critical roles in MADD disease progression and suggest novel treatment approaches that may ameliorate disease severity.     

Wetland Waterbird Food Resources Increased by Harvesting Invasive Cattails

The conservation of many freshwater marsh waterbirds (i.e., waterfowl, shorebirds, wading birds, and secretive marshbirds) in the Laurentian Great Lakes requires managing invasive emergent macrophytes, which degrade waterbird habitat by creating dense, litter-clogged stands, and excluding plants that produce nutritionally balanced and high-energy food (seeds, tubers, and submerged aquatic vegetation). The most commonly used management approach in the United States Great Lakes region involves the application of herbicides, which can stimulate waterbird forage plants but does not address the accumulation of plant litter, the underlying cause of plant community diversity loss and habitat degradation. We experimentally evaluated the effects of an alternative approach, harvesting invasive plants and their litter followed by flooding, on plant communities, focusing on the effects of these treatments to increase the abundance of high-energy wetland plants. At the Shiawassee National Wildlife Refuge in Michigan, USA, we experimentally treated an invasive cattail (Typha × glauca)-dominated wetland in August and September of 2016, 2017, and 2018, using a randomized block design with 4 blocks and 3 treatments (sediment surface harvest, above ground harvest, and control). We monitored the effects of these treatments on the abundance and dominance of waterbird forage-producing plants, plant diversity, and plant communities prior to (Jul 2016) and during the summer following each treatment (late Jul or early Aug 2017, 2018, and 2019). Additionally, we used pre- and post-treatment waterbird use-day data collected at the unit scale and compared values with satellite imagery-derived land cover changes. Compared to control plots, 3 years of harvesting and flooding significantly increased plant species diversity, increased the abundance of waterbird seed- and tuber-producing plant species by 5 times, and increased annual plant dominance by more than 10 times, while substantially reducing all measures of cattail and its litter. Use-days increased for total waterbirds, including waterfowl and dabbling ducks, following treatment. Cattail cover decreased and open water and non-cattail emergent vegetation cover increased. Harvesting invasive plant biomass coupled with flooding promoted a plant community composition and structure beneficial to waterbirds. © 2020 The Wildlife Society.