Recognizing normal reproductive biology: A comparative analysis of variability in menstrual cycle biomarkers in German and Bolivian women

The idealized “normal” menstrual cycle typically comprises a coordinated ebb and flow of hormones over a 28-day span with ovulation invariably shown at the midpoint. It's a pretty picture—but rare. Systematic studies have debunked the myth that cycles occur regularly about every 28 days. However, assumptions persist regarding the extent and normalcy of variation in other cycle biomarkers. The processes of judging which phenotypic variants are “normal” is context dependent. In everyday life, normal is that which is most commonly seen. In biomedicine normal is often defined as an arbitrarily bounded portion of the phenotype's distribution about its statistical mean. Standards thus defined in one population are problematic when applied to other populations; population specific standards may also be suspect. Rather, recognizing normal female reproductive biology in diverse human populations requires specific knowledge of proximate mechanisms and functional context. Such efforts should be grounded in an empirical assessment of phenotypic variability. We tested hypotheses regarding cycle biomarker variability in women from a wealthy industrialized population (Germany) and a resource-limited rural agropastoral population (Bolivia). Ovulatory cycles in both samples displayed marked but nonetheless comparable variability in all cycle biomarkers and similar means/medians for cycle and phase lengths. Notably, cycle and phase lengths are poor predictors of mid-luteal progesterone concentrations. These patterns suggest that global and local statistical criteria for “normal” cycles would be difficult to define. A more productive approach involves elucidating the causes of natural variation in ovarian cycling and its consequences for reproductive success and women's health

Mitochondrial polymorphism m.3017C>T of SHLP6 relates to heterothermy

Heterothermic thermoregulation requires intricate regulation of metabolic rate and activation of pro-survival factors. Eliciting these responses and coordinating the necessary energy shifts likely involves retrograde signalling by mitochondrial-derived peptides (MDPs). Members of the group were suggested before to play a role in heterothermic physiology, a key component of hibernation and daily torpor. Here we studied the mitochondrial single-nucleotide polymorphism (SNP) m.3017C>T that resides in the evolutionarily conserved gene MT-SHLP6. The substitution occurring in several mammalian orders causes truncation of SHLP6 peptide size from twenty to nine amino acids. Public mass spectrometric (MS) data of human SHLP6 indicated a canonical size of 20 amino acids, but not the use of alternative translation initiation codons that would expand the peptide. The shorter isoform of SHLP6 was found in heterothermic rodents at higher frequency compared to homeothermic rodents (p < 0.001). In heterothermic mammals it was associated with lower minimal body temperature (Tb, p < 0.001). In the thirteen-lined ground squirrel, brown adipose tissue—a key organ required for hibernation, showed dynamic changes of the steady-state transcript level of mt-Shlp6. The level was significantly higher before hibernation and during interbout arousal and lower during torpor and after hibernation. Our finding argues to further explore the mode of action of SHLP6 size isoforms with respect to mammalian thermoregulation and possibly mitochondrial retrograde signalling

Prevalence of drug-resistant minority variants in untreated HIV-1-infected individuals with and those without transmitted drug resistance detected by sanger sequencing

Minority variant human immunodeficiency virus type 1 (HIV-1) nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations are associated with an increased risk of virological failure during treatment with NNRTI-containing regimens. To determine whether individuals to whom variants with isolated NNRTI-associated drug resistance were transmitted are at increased risk of virological failure during treatment with a non-NNRTI-containing regimen, we identified minority variant resistance mutations in 33 individuals with isolated NNRTI-associated transmitted drug resistance and 49 matched controls. We found similar proportions of overall and nucleoside reverse transcriptase inhibitor-associated minority variant resistance mutations in both groups, suggesting that isolated NNRTI-associated transmitted drug resistance may not be a risk factor for virological failure during treatment with a non-NNRTI-containing regimen. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved

Bridging Microbial Functional Traits With Localized Process Rates at Soil Interfaces

In this review, we introduce microbially-mediated soil processes, players, their functional traits, and their links to processes at biogeochemical interfaces [e.g., rhizosphere, detritusphere, (bio)-pores, and aggregate surfaces]. A conceptual view emphasizes the central role of the rhizosphere in interactions with other biogeochemical interfaces, considering biotic and abiotic dynamic drivers. We discuss the applicability of three groups of traits based on microbial physiology, activity state, and genomic functional traits to reflect microbial growth in soil. The sensitivity and credibility of modern molecular approaches to estimate microbial-specific growth rates require further development. A link between functional traits determined by physiological (e.g., respiration, biomarkers) and genomic (e.g., genome size, number of ribosomal gene copies per genome, expression of catabolic versus biosynthetic genes) approaches is strongly affected by environmental conditions such as carbon, nutrient availability, and ecosystem type. Therefore, we address the role of soil physico-chemical conditions and trophic interactions as drivers of microbially-mediated soil processes at relevant scales for process localization. The strengths and weaknesses of current approaches (destructive, non-destructive, and predictive) for assessing process localization and the corresponding estimates of process rates are linked to the challenges for modeling microbially-mediated processes in heterogeneous soil microhabitats. Finally, we introduce a conceptual self-regulatory mechanism based on the flexible structure of active microbial communities. Microbial taxa best suited to each successional stage of substrate decomposition become dominant and alter the community structure. The rates of decomposition of organic compounds, therefore, are dependent on the functional traits of dominant taxa and microbial strategies, which are selected and driven by the local environment. Copyright © 2021 Blagodatskaya, Tarkka, Knief, Koller, Peth, Schmidt, Spielvogel, Uteau, Weber and Razavi

Validating the Biphilic Hypothesis of Nontrigonal Phosphorus(III) Compounds

Constraining σ3-P compounds in nontrigonal, entatic geometries has proven to be an effective strategy for promoting biphilic oxidative addition reactions more typical of transition metals. Although qualitative descriptions of the impact of structure and symmetry on σ3-P complexes have been proposed, electronic structure variations responsible for biphilic reactivity have yet to be elucidated experimentally. Reported here are P K-edge XANES data and complementary TDDFT calculations for a series of structurally modified P(N)3 complexes that both validate and quantify electronic structure variations proposed to give rise to biphilic reactions at phosphorus. These data are presented alongside experimentally referenced electronic structure calculations that reveal nontrigonal structures predicted to further enhance biphilic reactivity in σ3-P ligands and catalysts.NIH NIGMS (Grant GM114547)NSF (Grant CHE-1724505

Validating the Biphilic Hypothesis of Nontrigonal Phosphorus(III) Compounds

Constraining σ3-P compounds in nontrigonal, entatic geometries has proven to be an effective strategy for promoting biphilic oxidative addition reactions more typical of transition metals. Although qualitative descriptions of the impact of structure and symmetry on σ3-P complexes have been proposed, electronic structure variations responsible for biphilic reactivity have yet to be elucidated experimentally. Reported here are P K-edge XANES data and complementary TDDFT calculations for a series of structurally modified P(N)3 complexes that both validate and quantify electronic structure variations proposed to give rise to biphilic reactions at phosphorus. These data are presented alongside experimentally referenced electronic structure calculations that reveal nontrigonal structures predicted to further enhance biphilic reactivity in σ3-P ligands and catalysts.NIH NIGMS (Grant GM114547)NSF (Grant CHE-1724505