A divergent two-domain structure of the anti-Müllerian hormone prodomain.

TGFβ family ligands are synthesized as precursors consisting of an N-terminal prodomain and C-terminal growth factor (GF) signaling domain. After proteolytic processing, the prodomain typically remains noncovalently associated with the GF, sometimes forming a high-affinity latent procomplex that requires activation. For the TGFβ family ligand anti-Müllerian hormone (AMH), the prodomain maintains a high-affinity interaction with its GF that does not render it latent.

Evidence of a Catalytic Dyad in F-Dependent Glucose-6-phosphate Dehydrogenase from .

F-dependent glucose-6-phosphate dehydrogenase (FGD) catalyzes the conversion of glucose-6-phosphate (G6P) to 6-phosphogluconolactone, using cofactor F as the hydride transfer acceptor. Our previous pH dependence studies suggested that E109 serves as an active site acid, donating a proton to the N-1 position of F, while leaving the role of H40 unanswered, which was previously suggested to serve as the active site base. This work utilizes thermodynamic and kinetic studies to elucidate additional mechanistic details concerning the roles of H40 and E13.

Structural Basis of Non-Latent Signaling by the Anti-Müllerian Hormone Procomplex.

Most TGFβ family ligands exist as procomplexes consisting of a prodomain noncovalently bound to a growth factor (GF); Whereas some prodomains confer latency, the Anti-Müllerian Hormone (AMH) prodomain maintains a remarkably high affinity for the GF yet remains active. Using single particle EM methods, we show the AMH prodomain consists of two subdomains: a vestigial TGFβ prodomain-like fold and a novel, helical bundle GF-binding domain, the result of an exon insertion 450 million years ago, that engages both receptor epitopes. When associated with the prodomain, the AMH GF is distorted into a strained, open conformation whose closure upon bivalent binding of AMHR2 displaces the prodomain through a conformational shift mechanism to allow for signaling.

Enhancing radioprotection: A chitosan-based chelating polymer is a versatile radioprotective agent for prophylactic and therapeutic interventions against radionuclide contamination.

To mitigate the risk of radioactive isotope dissemination, the development of preventative and curative measures is of particular interest. For mass treatment, the developed solution must be easily administered, preferably orally, with effective, nontoxic decorporating properties against a wide range of radioactive isotopes. Currently, most orally administered chelation therapy products are quickly absorbed into the blood circulation, where chelation of the radioactive isotope is a race against time due to the short circulation half-life of the therapeutic.

Correlating fluorescence microscopy, optical and magnetic tweezers to study single chiral biopolymers such as DNA.

Biopolymer topology is critical for determining interactions inside cell environments, exemplified by DNA where its response to mechanical perturbation is as important as biochemical properties to its cellular roles. The dynamic structures of chiral biopolymers exhibit complex dependence with extension and torsion, however the physical mechanisms underpinning the emergence of structural motifs upon physiological twisting and stretching are poorly understood due to technological limitations in correlating force, torque and spatial localization information. We present COMBI-Tweez (Combined Optical and Magnetic BIomolecule TWEEZers), a transformative tool that overcomes these challenges by integrating optical trapping, time-resolved electromagnetic tweezers, and fluorescence microscopy, demonstrated on single DNA molecules, that can controllably form and visualise higher order structural motifs including plectonemes.

Activin E is a transforming growth factor β ligand that signals specifically through activin receptor-like kinase 7.

Activins are one of the three distinct subclasses within the greater Transforming growth factor β (TGFβ) superfamily. First discovered for their critical roles in reproductive biology, activins have since been shown to alter cellular differentiation and proliferation. At present, members of the activin subclass include activin A (ActA), ActB, ActC, ActE, and the more distant members myostatin and GDF11.

GDF11 and aging biology - controversies resolved and pending.

Since the exogenous administration of GDF11, a TGF-ß superfamily member, was reported to have beneficial effects in some models of human disease, there have been many research studies in GDF11 biology. However, many studies have now confirmed that exogenous administration of GDF11 can improve physiology in disease models, including cardiac fibrosis, experimental stroke, and disordered metabolism. GDF11 is similar to GDF8 (also called Myostatin), differing only by 11 amino acids in their mature signaling domains.

Heterogeneity in Neutrophil Extracellular Traps from Healthy Human Subjects.

Neutrophil extracellular traps (NETs), a key component of early defense against microbial infection, are also associated with tissue injury. NET composition has been reported to vary with some disease states, but the composition and variability of NETs across many healthy subjects provide a critical comparison that has not been well investigated. We evaluated NETs from twelve healthy subjects of varying ages isolated from multiple blood draws over a three-and-one-half-year period to delineate the variability in extracellular DNA, protein, enzymatic activities, and susceptibility to protease inhibitors.

Characterization of the molecular mechanisms that govern anti-Müllerian hormone synthesis and activity.

The roles of anti-Müllerian hormone (AMH) continue to expand, from its discovery as a critical factor in sex determination, through its identification as a regulator of ovarian folliculogenesis, its use in fertility clinics as a measure of ovarian reserve, and its emerging role in hypothalamic-pituitary function. In light of these actions, AMH is considered an attractive therapeutic target to address diverse reproductive needs, including fertility preservation. Here, we set out to characterize the molecular mechanisms that govern AMH synthesis and activity.

Tetrameric UvrD Helicase Is Located at the E. Coli Replisome due to Frequent Replication Blocks.

DNA replication in all organisms must overcome nucleoprotein blocks to complete genome duplication. Accessory replicative helicases in Escherichia coli, Rep and UvrD, help remove these blocks and aid the re-initiation of replication. Mechanistic details of Rep function have emerged from recent live cell studies; however, the division of UvrD functions between its activities in DNA repair and role as an accessory helicase remain unclear in live cells.

Heterogeneity in Neutrophil Extracellular Traps from Healthy Human Subjects.

Neutrophil Extracellular Traps (NETs), a key component of early defense against microbial infection, are also associated with tissue injury. NET composition has been reported to vary with some disease states, but the composition and variability of NETs across many healthy subjects provides a critical comparison that has not been well investigated. We evaluated NETs from twelve healthy subjects of varying ages isolated from multiple blood draws over a three and one half-year period to delineate the variability in extracellular DNA, protein, enzymatic activities, and susceptibility to protease inhibitors.

Activin E is a TGFβ ligand that signals specifically through activin receptor-like kinase 7.

Activins are one of the three distinct subclasses within the greater Transforming Growth Factor β (TGFβ) superfamily. First discovered for their critical roles in reproductive biology, activins have since been shown to alter cellular differentiation and proliferation. At present, members of the activin subclass include activin A (ActA), ActB, ActC, ActE, and the more distant members myostatin and GDF11.

Testing evolutionary conflict theories for sexual and physical intimate partner violence in Sub-Saharan Africa.

Intimate partner violence (IPV) refers to physical, sexual and psychological violence. Here an evolutionary approach is used to compare risk factors for male-to-female IPV perpetration, analysing physical and sexual IPV separately. Two hypotheses based on sexual conflict theory have been applied to IPV perpetration, but they remain largely untested using empirical data: (a) men perpetrate IPV in response to a perceived threat to their paternity certainty; and (b) IPV is caused by men pursuing a higher fertility optima than their partners, either within marriage (reproductive coercion) or outside marriage (paternal disinvestment).

Combating lead and cadmium exposure with an orally administered chitosan-based chelating polymer.

Heavy metals present a threat to human health, even at minimal concentrations within the body. One source of exposure is due to the consumption of low-level contaminated foodstuff and water. Lead and cadmium have been shown to be absorbed by and accumulate within organs like the kidneys and liver, and they have also been associated to many diseases including cardiovascular disease and kidney dysfunction as well as developmental disorders and neurodegenerative diseases.

Molecular Mechanisms of AMH Signaling.

Anti-Müllerian Hormone (AMH) is a secreted glycoprotein hormone with critical roles in reproductive development and regulation. Its chemical and mechanistic similarities to members of the Transforming Growth Factor β (TGF-β) family have led to its placement within this signaling family. As a member of the TGF-β family, AMH exists as a noncovalent complex of a large N-terminal prodomain and smaller C-terminal mature signaling domain.

Oral Administration of Coronavirus Spike Protein Provides Protection to Newborn Pigs When Challenged with PEDV.

To investigate whether oral administration of maize-produced S antigen can provide passive immunity to piglets against porcine epidemic diarrhea virus (PEDV), 16 pregnant sows were randomly assigned to one of four treatments: (1) injection of PEDV vaccine (INJ), (2) maize grain without S protein (CON), (3) maize grain containing low dose of S antigen (LOV) and (4) maize grain containing a high dose of S antigen (HOV). Vaccines were administered on days 57, 85 and 110 of gestation. Sows' serum and colostrum were collected at farrowing and milk on day 6 post-challenge to quantify neutralizing antibodies (NABs) and cytokines.

Co(NCS)(abpt) and Ni(NCS)(abpt) [abpt is 4-amino-3,5-bis(pyridin-2-yl)-1,2,4-triazole]: structural characterization of polymorphs A and B.

The synthesis and structures of bis[4-amino-3,5-bis(pyridin-2-yl)-1,2,4-triazole-κN,N]bis(thiocyanato-κN)cobalt(II), [Co(NCS)(CHN)] or Co(NCS)(abpt), and bis[4-amino-3,5-bis(pyridin-2-yl)-1,2,4-triazole-κN,N]bis(thiocyanato-κN)nickel(II), [Ni(NCS)(CHN)] or Ni(NCS)(abpt), are reported. In both cases, two polymorphs, A and B, were identified and structurally characterized. For both polymorphs, the structures obtained with the different metals, i.

No relationship found between female genital cutting and intimate partner violence across six sub-Saharan African countries.

Female genital cutting (FGC) and intimate partner violence (IPV) are highly prevalent forms of violence against women, and the UN has encouraged strengthening policy linkages between FGC and IPV programme work (UN Women, . UN Women, 2017a). However few studies have examined the relationship between these behaviours.

Selected solid-state behaviour of three di-tert-butyl-substituted N-salicylideneaniline derivatives: temperature-induced phase transitions and chromic behaviour.

The synthesis, single-crystal structures and chromic behaviour of three related Schiff bases, namely, (E)-2,4-di-tert-butyl-6-{[(4-fluorophenyl)imino]methyl}phenol, CHFNO, 1, (E)-2,4-di-tert-butyl-6-{[(4-chlorophenyl)imino]methyl}phenol, CHClNO, 2, and (E)-6-{[(4-bromophenyl)imino]methyl}-2,4-di-tert-butylphenol, CHBrNO, 3, are reported. Two polymorphs of 1 were obtained, which were found to have different photochromic properties. Schiff bases 2 and 3 were found to be isostructural and underwent a phase transition upon cooling which was attributed to the dynamic disorder in one of the tert-butyl groups resolving at low temperature.

Low temperature insights into the crystal and magnetic structure of a neutral radical ferromagnet.

The crystal structure of the radical ferromagnet 1a at 2 K reveals a contraction in the unit cell constant which, at the molecular level, translates into a decrease in slippage of the radical π-stacks and an increase in ferromagnetic exchange interactions along the stacking axis. The results of BS-DFT calculations using long-range corrected functionals are consistent with an overall ferromagnetic topology.

Interplay between spin crossover and proton migration along short strong hydrogen bonds.

The iron(ii) salt [Fe(bpp)](isonicNO)·HisonicNO·5HO () (bpp = 2,6-bis(pyrazol-3-yl)pyridine; isonicNO = isonicotinate N-oxide anion) undergoes a partial spin crossover (SCO) with symmetry breaking at = 167 K to a mixed-spin phase (50% high-spin (HS), 50% low-spin (LS)) that is metastable below = 116 K. Annealing the compound at lower temperatures results in a 100% LS phase that differs from the initial HS phase in the formation of a hydrogen bond (HB) between two water molecules (O4W and O5W) of crystallisation. Neutron crystallography experiments have also evidenced a proton displacement inside a short strong hydrogen bond (SSHB) between two isonicNO anions.

Exosomal integrins and their influence on pancreatic cancer progression and metastasis.

As one of the most lethal and untreatable types of cancer so far, pancreatic cancer is not benefitting from advancements in research. Despite all the efforts, this malignancy is still very difficult to diagnose in time, resistant to treatments, and prone to relapses. The appearance of metastasis-notoriously difficult to fight and a signal of unfortunate prognosis-is the event most dreaded by every cancer patient, especially by those with pancreatic cancer.