SUMMARY1. Observations were made on the excretion of calcium and magnesium by the sheep's kidney following manipulation of the acid-base status.2. Intravascular administration of a synthetic solution resembling saliva abolished the naturally occurring acidosis in sheep during feeding, and it also prevented the normal onset of post-prandial hypercalciuria and hypermagnesiuria.3. Non-respiratory acidosis (induced by infusion of hydrochloric acid) and respiratory acidosis arising from inhalation of 6 % (v/v) C02 in air both caused an acute increase in calcium excretion.4. Measurement of filtered loads showed that feeding exerted an effect on the functional characteristics of the sheep's kidney. The renal clearances of calcium and magnesium increased, whereas sodium clearance decreased.5. Experimental conditions were arranged so that variations in acidbase status could be imposed at a time when the filtered load of calcium was declining.6. With hydrochloric acid-acidosis the renal excretion of calcium increased, despite a steady fall in the filtered load. With sodium bicarbonate alkalosis, the filtered load and the renal excretion of calcium decreased in unison. 7. These variations in calcium excretion were not accompanied by corresponding changes in the excretion of sodium.8. It is concluded that the renal tubules in the sheep are sensitive to acid-base status and that they respond to a lowering of the blood pH by decreasing the tubular reabsorption of filtered calcium.

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IMPORTANCE Cardiovascular (CV) mortality has declined for more than 3 decades in the US. However, differences in declines among residents at a US county level are not well characterized. OBJECTIVETo identify unique county-level trajectories of CV mortality in the US during a 35-year study period and explore county-level factors that are associated with CV mortality trajectories. DESIGN, SETTING, AND PARTICIPANTS This longitudinal cross-sectional analysis of CV mortality trends used data from 3133 US counties from 1980 to 2014. County-level demographic, socioeconomic, environmental, and health-related risk factors were compiled. Data were analyzed from December 2019 to September 2021.EXPOSURES County-level characteristics, collected from 5 county-level data sets. MAIN OUTCOMES AND MEASURESCardiovascular mortality data were obtained for 3133 US counties from 1980 to 2014 using age-standardized county-level mortality rates from the Global Burden of Disease study. The longitudinal K-means approach was used to identify 3 distinct clusters based on underlying mortality trajectory. Multinomial logistic regression models were constructed to evaluate associations between county characteristics and cluster membership.

The previously described fusion protein BLAH(6) (Marques JA et al.,Thromb Haemost 2001; 86: 902-8) is a recombinant protein that combines the small disintegrin barbourin with hexahistidine-tagged rabbit serumalbumin (RSA) produced in Pichia pastoris yeast. We sought to determine: (1) if BLAH(6) was immunogenic; and (2) if its barbourin domain could be productively replaced with smaller peptides. Purified BLAH(6) was injected into rabbits, and anti-barbourin antibodies were universally detected in plasma 28 days later; BLAH(6) was, however, equally effective in reducing platelet aggregation in both naive and pre-treated rabbits. Thrombocytopenia was not observed, and complexing BLAH(6) to alpha(IIb)beta(3) had no effect on antibody detection. The barbourin moiety of BLAH(6) was replaced with each of four sequences: Pep I (VCKGDWPC); PepII (VCRGDWPC); PepIII (bar-bourin 41-54); and PepIV (LPSPGDWR). The corresponding fusion proteins were tested for their ability to inhibit ADP-induced platelet aggregation. PepIII-LAH(6) inhibited neither rabbit nor human platelets. PepI-LAH(6) and PepIV-LAH(6) inhibited rabbit platelet aggregation as effectively as BLAH(6), but PepIV-LAH(6) did not inhibit human platelet aggregation. PepI-LAH(6) and PepIILAH(6) inhibited human platelet aggregation with IC(50)s 10- and 20-fold higher than BLAH(6). Cross-immunoprecipitation assays with human platelet lysates confirmed that all proteins and peptides interacted with the platelet integrin alpha(IIb)beta(3), but with greatly varying affinities. Our results suggest that the antiplatelet activity of BLAH(6) can be retained in albumin fusion proteins in which smaller peptides replace the barbourin domain; these proteins may be less immunogenic than BLAH(6).

This paper investigates the role of negation in grammaticalization in Iquito, an endangered Zaparoan language of the Peruvian Amazon. Iquito has a verb, pajɨɨni, which has undergone two paths of grammaticalization only in negated clauses. First, pajɨɨni has grammaticalized from “learn” to “be able to.” Subsequently, it is undergoing grammaticalization from an ability verb to a future auxiliary. Given that ability verbs are an uncommon source for future auxiliaries (Bybee et al. 1994), this study provides a detailed case study of this rare path. Our analysis of Iquito demonstrates that grammaticalization paths are not limited to affirmative contexts and may behave differently depending on the polarity of the utterance.