Pheromonal influences on sociosexual behavior in young women

Abstract A double-blind, placebo-controlled study of a synthesized putative female pheromone was conducted with regularly menstruating, university women (N = 36, mean age = 27.8). The pheromone formula was derived from earlier work investigating the underarm secretions of fertile, sexually active, heterosexual women. A vial of either synthesized pheromone or placebo was selected blindly and added to a subject's perfume. Subjects recorded seven sociosexual behaviors and reported them weekly across three menstrual cycles. Beginning with Day 8 of each cycle, the first cycle contained a 2-week baseline period followed by an experimental period of as many as 3 weeks each from the next two cycles for a maximum of 6 weeks. The 19 pheromone and 17 placebo subjects did not differ significantly in age, weight, body mass index, dating status or ethnicity nor in reported accuracy, back-filling data, perception of a positive effect or perfume use. Placebo subjects were significantly taller than pheromone subjects. Except for male approaches, subjects did not differ significantly at baseline in average weekly sociosexual behaviors. A significantly greater proportion of pheromone users compared with placebo users increased over baseline in frequency of sexual intercourse, sleeping next to a partner, formal dates and petting/affection/kissing but not in frequency of male approaches, informal dates or masturbation. Three or more sociosexual behaviors increased over baseline for 74% of pheromone users compared with 23% of placebo users. We conclude that this synthesized pheromone formula acted as a sex attractant pheromone and increased the sexual attractiveness of women to men.

A short-term comparison of wheat straw and poplar wood chips used as litter in tiestalls on hygiene, milk, and behavior of lactating dairy cows

A short-term study was conducted to compare the effect of using poplar wood chips (PWC) instead of wheat straw (WS) litter in dairy cows. A total of 38 lactating Holstein cows (204 ± 119 days in milk, 26.9 ± 6.5 kg of milk yield [MY]) were housed in a tiestall farm for a 10-d trial including 5 d of adaptation followed by 5 sampling days (from d 5 to 10). Cows were divided into 2 homogeneous groups: one group was bedded with WS, and the second with PWC. Both litter materials were provided in the amount of 7 kg/stall per d. Each group was composed of 3 subgroups of 6 or 7 cows; the subgroups were physically separated along the feeding line by wooden boards. During the sampling days, fecal composition, used litter composition, and bacterial count (Clostridium spp., Salmonella spp., Escherichia coli, Lactobacillus, and total bacterial count) were analyzed by subgroup twice a day. On d 1 and from d 5 to 10, udder hygiene score and cow cleanliness score were also evaluated individually twice a day. Meanwhile MY, milk hygiene (total bacterial count [TBC], coliform bacterial count [CBC], and spore-forming unit [SFU]) and quality were measured and analyzed from 9 animals per group. Moreover, individual animal behavior (body position and behavioral traits) and subgroup dry matter intake were measured on d 9 and 10. Fecal dry matter did not differ between groups, PWC had the lowest used litter moisture and N content favoring the highest clean cow frequency, but also gave rise to the greatest used litter microbial contamination. The MY, milk quality, TBC, SFU, and CBC were similar. The lying behavior frequency was similar between groups. However, the PWC group showed the lowest sleeping frequency, the highest frequency of other behaviors (including discomfort signs), and the lowest dry matter intake. However, despite this apparent reduction in cow comfort, no biologically important differences were observed in this short-term study between cows on PWC and WS in milk production or hygiene

E46K-like α-synuclein mutants increase lipid interactions and disrupt membrane selectivity

Parkinson's disease (PD) is one of the most common neurodegenerative disorders and both genetic and histopathological evidence have implicated the ubiquitous presynaptic protein α-synuclein (αSyn) in its pathogenesis. Recent work has investigated how disrupting αSyn's interaction with membranes triggers trafficking defects, cellular stress, and apoptosis. Special interest has been devoted to a series of mutants exacerbating the effects of the E46K mutation (associated with autosomal dominant PD) through homologous E-to-K substitutions in αSyn's N-terminal region (i.e. E35K, E61K). Such E46K-like mutants have been shown to cause dopaminergic neuron loss and severe, yet L-DOPA-responsive, motor defects in mouse overexpression models, presenting enormous translational potential for PD and other "synucleinopathies". In this work, using a variety of biophysical techniques, we characterize the molecular pathology of E46K-like αSyn mutants by studying their structure and membrane-binding and remodeling abilities. We find that, although a slight increase in the mutants' avidity for synaptic vesicle-like membranes can be detected, most of their deleterious effects are connected to their complete disruption of αSyn's curvature selectivity. Indiscriminate binding can shift αSyn's subcellular localization away from its physiological interactants at the synaptic bouton toward trafficking vesicles and organelles, as observed in E46K-like cellular and murine models, as well as in human pathology. In conclusion, our findings suggest that a loss of curvature selectivity, rather than increased membrane affinity, could be the critical dyshomeostasis in synucleinopathies

Osteocalcin (bone GLA protein) levels, vascular calcifications, vertebral fractures and mortality in hemodialysis patients with diabetes mellitus

Background and aims: Diabetes mellitus is recognized as one of the major causes of end stage kidney disease. Bone Gla protein (BGP) is a vitamin K-dependent protein involved in bone mineralization and vascular calcifications (VC). Our goal was to characterize BGP and undercarboxylated BGP (ucBGP) in DM patients on HD, compared to HD patients without DM, and their association with vascular and bone disease. Methods: 387 HD patients from 18 dialysis centers in Italy. Associations of DM, levels of BGP, vitamin D and VC were evaluated. Time-to-event analysis for all-cause mortality was performed by the Kaplan\u2013Meier. Results: Patients with DM had lower levels of total BGP (139.00 vs. 202.50 mcg/L, p < 0.001), 25(OH)D (23.4 vs. 30.2 ng/ml, p < 0.001), and ucBGP (9.24 vs. 11.32 mcg/L, p = 0.022). In regression models, the geometric means of total BGP and ucBGP were 19% (p = 0.009) and 26% (p = 0.034) lower in diabetic patients. In univariate Cox regression analysis, DM patients had a higher risk of all-cause mortality (HR:1.83, 95% CI 1.13\u20132.96, p = 0.014). Adjustment for confounders confirmed the significant DM-mortality link. We included VC and warfarin into the Cox model, the DM-mortality link was no longer significant, suggesting a role of these risk factors as causal mediators leading to increased mortality in dialysis patients. Conclusions: HD patients have an increased mortality risk associated with DM. Furthermore, we found an association between DM and decreased BGP levels. Although our study does not support the notion that BGP levels act as mediator in the DM-mortality link, to our knowledge this is the first study in HD patients suggesting a potential protective role of BGP in the bone, endocrine and vascular pathway

A novel likely pathogenetic variant p.(Cys235Arg) of the MEN1 gene in multiple endocrine neoplasia type 1 with multifocal glucagonomas

PURPOSE: Multiple endocrine neoplasia type 1 (MEN1) is a hereditary endocrine syndrome caused by pathogenic variants in MEN1 tumor suppressor gene. Diagnosis is commonly based on clinical criteria and confirmed by genetic testing. The objective of the present study was to report on a MEN1 case characterized by multiple pancreatic glucagonomas, with particular concern on the possible predisposing genetic defects. METHODS: While conducting an extensive review of the most recent scientific evidence on the unusual glucagonoma familial forms, we analyzed the MEN1 gene in a 35-year-old female with MEN1, as well as her son and daughter, using Sanger and next-generation sequencing (NGS) approaches. We additionally explored the functional and structural consequences of the identified variant using in silico analyses. RESULTS: NGS did not show any known pathogenic variant in the tested regions. However, a new non-conservative variant in exon 4 of MEN1 gene was found in heterozygosity in the patient and in her daughter, resulting in an amino acid substitution from hydrophobic cysteine to hydrophilic arginine at c.703T > C, p.(Cys235Arg). This variant is absent from populations databases and was never reported in full papers: its characteristics, together with the high specificity of the patient's clinical phenotype, pointed toward a possible causative role. CONCLUSION: Our findings confirm the need for careful genetic analysis of patients with MEN1 and establish a likely pathogenic role for the new p.(Cys235Arg) variant, at least in the rare subset of MEN1 associated with glucagonomas

In vitro and in vivo modeling of lipid bioaccessibility and digestion from almond muffins: the importance of the cell-wall barrier mechanism

This study compares in vitro and in vivo models of lipid digestion from almond particles within a complex food matrix (muffins) investigating whether the cell-wall barrier regulates the bioaccessibility of nutrients within this matrix. Muffins containing small (AF) or large (AP) particles of almond were digested in triplicate using an in vitro dynamic gastric model (DGM, 1 h) followed by a static duodenal digestion (8 h). AF muffins had 97.1 ± 1.7% of their lipid digested, whereas AP muffins had 57.6 ± 1.1% digested. In vivo digestion of these muffins by an ileostomy volunteer (0–10 h) gave similar results with 96.5% and 56.5% lipid digested, respectively. The AF muffins produced a higher postprandial triacylglycerol iAUC response (by 61%) than the AP muffins. Microstructural analysis showed that some lipid remained encapsulated within the plant tissue throughout digestion. The cell-wall barrier mechanism is the main factor in regulating lipid bioaccessibility from almond particles

Tobacco Rattle Virus Vector: A Rapid and Transient Means of Silencing Manduca sexta Genes by Plant Mediated RNA Interference

Background: RNAi can be achieved in insect herbivores by feeding them host plants stably transformed to express double stranded RNA (dsRNA) of selected midgut-expressed genes. However, the development of stably transformed plants is a slow and laborious process and here we developed a rapid, reliable and transient method. We used viral vectors to produce dsRNA in the host plant Nicotiana attenuata to transiently silence midgut genes of the plant’s lepidopteran specialist herbivore, Manduca sexta. To compare the efficacy of longer, undiced dsRNA for insect gene silencing, we silenced N. attenuata’s dicer genes (NaDCL1- 4) in all combinations in a plant stably transformed to express dsRNA targeting an insect gene. Methodology/Principal Findings: Stable transgenic N. attenuata plants harboring a 312 bp fragment of MsCYP6B46 in an inverted repeat orientation (ir-CYP6B46) were generated to produce CYP6B46 dsRNA. After consuming these plants, transcripts of CYP6B46 were significantly reduced in M. sexta larval midguts. The same 312 bp cDNA was cloned in an antisense orientation into a TRV vector and Agro-infiltrated into N. attenuata plants. When larvae ingested these plants, similar reductions in CYP6B46 transcripts were observed without reducing transcripts of the most closely related MsCYP6B45. We used this transient method to rapidly silence the expression of two additional midgut-expressed MsCYPs. CYP6B46 transcripts were further reduced in midguts, when the larvae fed on ir-CYP6B46 plants transiently silenced for tw

LRR-RLK family from two Citrus species: Genome-wide identification and evolutionary aspects

Background: Leucine-rich repeat receptor-like kinases (LRR-RLKs) represent the largest subfamily of plant RLKs. The functions of most LRR-RLKs have remained undiscovered, and a few that have been experimentally characterized have been shown to have important roles in growth and development as well as in defense responses. Although RLK subfamilies have been previously studied in many plants, no comprehensive study has been performed on this gene family in Citrus species, which have high economic importance and are frequent targets for emerging pathogens. In this study, we performed in silico analysis to identify and classify LRR-RLK homologues in the predicted proteomes of Citrus clementina (clementine) and Citrus sinensis (sweet orange). In addition, we used large-scale phylogenetic approaches to elucidate the evolutionary relationships of the LRR-RLKs and further narrowed the analysis to the LRR-XII group, which contains several previously described cell surface immune receptors. Results: We built integrative protein signature databases for Citrus clementina and Citrus sinensis using all predicted protein sequences obtained from whole genomes. A total of 300 and 297 proteins were identified as LRR-RLKs in C. clementina and C. sinensis, respectively. Maximum-likelihood phylogenetic trees were estimated using Arabidopsis LRR-RLK as a template and they allowed us to classify Citrus LRR- 34 RLKs into 16 groups. The LRR-XII group showed a remarkable expansion, containing approximately 150 paralogs encoded in each Citrus genome. Phylogenetic analysis also demonstrated the existence of two distinct LRR-XII clades, each one constituted mainly by RD and non-RD kinases. We identified 68 orthologous pairs from the C. clementina and C. sinensis LRR-XII genes. In addition, among the paralogs, we identified a subset of 78 and 62 clustered genes probably derived from tandem duplication events in the genomes of C. clementina and C. sinensis, respectively. Conclusions: This work provided the first comprehensive evolutionary analysis of the LRR-RLKs in Citrus. A large expansion of LRR-XII in Citrus genomes suggests that it might play a key role in adaptive responses in host-pathogen co-evolution, related to the perennial life cycle and domestication of the citrus crop species