Maternal high-fat high-sugar diet impairs bone quality and strength but not cartilage in aging mice.

Osteoarthritis (OA) is a prevalent aging disorder of synovial joints and recent work suggests that a parental high-fat diet increases OA severity following joint injury in offspring. We hypothesized that a maternal high-fat high-sugar (HFHS) diet would promote spontaneous osteoarthritis-related cartilage and bone changes in 1-year-old offspring. Female C57BL/6 J mice were placed on either a chow control or HFHS diet for 6 weeks before mating to a chow-fed C57BL/6 J male and maintained on their assigned diets throughout pregnancy and lactation.

Fracture or Not: An Easily Mistaken Benign Finding in a Tuberous Sclerosis Patient.

Tuberous sclerosis (TSC) is a rare autosomal dominant disorder that can affect multiple organ systems, including the brain, heart, lungs, and skin. Cutaneous manifestations are common, including ungual fibromas, however, these may be mistaken for other pathologies. Here, we present the case of a 14-year-old with TSC complaining of traumatic left little finger pain.

The autophagy protein, ATG14 safeguards against unscheduled pyroptosis activation to enable embryo transport during early pregnancy.

Recurrent pregnancy loss (RPL), characterized by two or more failed clinical pregnancies, poses a significant challenge to reproductive health. In addition to embryo quality and endometrial function, proper oviduct function is also essential for successful pregnancy establishment. Therefore, structural abnormalities or inflammation resulting from infection in the oviduct may impede the transport of embryos to the endometrium, thereby increasing the risk of miscarriage.

Process intensification for the production of a C-tagged antimicrobial peptide in Escherichia coli - First steps toward a platform technology.

The production of antimicrobial peptides/proteins (AMPs) in sufficient quantities for clinical evaluation is challenging because complex peptides are unsuitable for chemical synthesis, natural sources have low yields, and heterologous systems often have low expression levels or require product-specific process adaptations. Here we describe the production of a complex AMP, the insect metalloproteinase inhibitor (IMPI), by adding a C-terminal C-tag to increase the yield compared to the unmodified peptide. We used a design of experiments approach for process intensification in Escherichia coli Rosetta-gami 2(DE3)pLysS cells and achieved a yield of 260 mg L, which is up to 30-fold higher than previously reported.

Hot-Water Hemicellulose Extraction from Fruit Processing Residues.

Hemicelluloses are an abundant biopolymer resource with interesting properties for applications in coatings and composite materials. The objective of this investigation was to identify variables of industrially relevant extraction processes that increase the purity of hemicelluloses extracted from fruit residues. Our main finding is that extraction with subcritical water, followed by precipitation with alcohol, can be adjusted to yield products with a purity of at least 90%.

Conditional knockout of leptin receptor in the female reproductive tract reduces fertility due to parturition defects in mice.

Leptin is required for fertility, including initiation of estrous cycles. It is therefore challenging to assess the role of leptin signaling during pregnancy. Although neuron-specific transgene approaches suggest that leptin signaling in the central nervous system is most important, experiments with pharmacologic inhibition of leptin in the uterus or global replacement of leptin during pregnancy suggest leptin signaling in the reproductive tract may be required.

Adipose tissue is a critical regulator of osteoarthritis.

Osteoarthritis (OA), the leading cause of pain and disability worldwide, disproportionally affects individuals with obesity. The mechanisms by which obesity leads to the onset and progression of OA are unclear due to the complex interactions among the metabolic, biomechanical, and inflammatory factors that accompany increased adiposity. We used a murine preclinical model of lipodystrophy (LD) to examine the direct contribution of adipose tissue to OA.

Fecundity is impaired in a mouse model of osteogenesis imperfecta.

Osteogenesis imperfecta (OI), or brittle bone disease, is most often caused by mutations in genes encoding type I collagen or proteins that process it. Women with OI have a small, but significant increase in risk of serious pregnancy complications including uterine rupture. Here, the OI mouse, Col1a2 , was used to examine the effects of collagen mutation on establishment and maintenance of pregnancy.

Is Obesity a Disease of Stem Cells?

Obesity disrupts physiological homeostasis and alters both systemic and local microenvironments that impact stem cell plasticity and impair regenerative capacity. We present growing evidence that reveals the bidirectionality of obesity-induced stem cell dysfunction and how the molecular changes in stem cells residing in obese environments may accelerate disease severity.

Leprdb/+ Dams Protect Wild-type Male Offspring Bone Strength from the Detrimental Effects of a High-Fat Diet.

The prevalence of maternal obesity is increasing at an alarming rate and increases the life-long risk of developing cardiometabolic disease in adult offspring. Leptin, an adipokine, is systemically elevated in the obese milieu. We recently showed that maternal hyperleptinemia without obesity improves offspring insulin sensitivity and glucose tolerance while protecting against weight gain on a high-fat, high-sugar (HFD).

The autophagy protein, FIP200 (RB1CC1) mediates progesterone responses governing uterine receptivity and decidualization†.

Successful establishment of pregnancy depends on steroid hormone-driven cellular changes in the uterus during the peri-implantation period. To become receptive to embryo implantation, uterine endometrial stromal cells (ESCs) must transdifferentiate into decidual cells that secrete factors necessary for embryo survival and trophoblast invasion. Autophagy is a key homeostatic process vital for cellular homeostasis.

The Autophagy Gene Atg16L1 is Necessary for Endometrial Decidualization.

Uterine receptivity is critical for establishing and maintaining pregnancy. For the endometrium to become receptive, stromal cells must differentiate into decidual cells capable of secreting factors necessary for embryo survival and placental development. Although there are multiple reports of autophagy induction correlated with endometrial stromal cell (ESC) decidualization, the role of autophagy in decidualization has remained elusive.

Homozygous missense variant in BMPR1A resulting in BMPR signaling disruption and syndromic features.

Background: The bone morphogenetic protein (BMP) pathway is known to play an imperative role in bone, cartilage, and cardiac tissue formation. Truncating, heterozygous variants, and deletions of one of the essential receptors in this pathway, Bone Morphogenetic Protein Receptor Type1A (BMPR1A), have been associated with autosomal dominant juvenile polyposis. Heterozygous deletions have also been associated with cardiac and minor skeletal anomalies.

Selective rickets from localized advanced maturation-a case report.

An unusual cause of rickets is illustrated by a patient with infantile multisystem inflammatory disease who, by age 2 years and 4 months, developed striking radiographic and clinical rickets restricted to those joints involved by the inflammatory process. The locally increased vascularity from his inflammation led to increased maturation at those sites so rapid as to override the usual enchondral calcification, thus causing a rickets pattern. Other sites, such as the proximal humeri, lacking any inflammation, showed no increased maturation rate and did not manifest local rickets.

Postmortem distribution and redistribution of MDAI and 2-MAPB in blood and alternative matrices.

Intoxication cases involving new psychoactive substances (NPS) provide several challenges for forensic toxicologists as data on pharmacodynamic and pharmacokinetic properties are lacking, especially on potency and toxicity. Furthermore, reference values and information on postmortem redistribution (PMR) do not exist so far for most NPS. A fatal case involving the amphetamine-derivatives MDAI (5,6-methylenedioxy-2-aminoindane) and 2-MAPB (1-(benzofuran-2-yl)-N-methylpropan-2-amine) was investigated at the Zurich Institute of Forensic Medicine.

Developmental and Transmittable Origins of Obesity-Associated Health Disorders.

The current global obesity pandemic is clearly linked to both the increasing prevalence of, and preference for, foods high in calories, specifically fat and sucrose, and declining levels of daily physical activity. A less commonly discussed possible explanation is that risk of obesity begins in utero as a result of developmental plasticity during early life. This idea fits into the broader Developmental Origins of Health and Diseases (DOHAD) hypothesis, which holds that stressful in utero exposure manifests as disease in adulthood.

Women Reigious Unite To Eradicate Trafficking.

The history of women's religious congregations is a history of addressing unmet needs. The founders and foundresses of our communities read the signs of their times and gathered women together to serve God and God's most vulneiable people. When the Second Vatican Council invited us to re-examine our founding charisms in light of the needs of our times, we rediscovered our own preferential option for those who are poor, often with a special care for women and children.

Decreasing maternal myostatin programs adult offspring bone strength in a mouse model of osteogenesis imperfecta.

During fetal development, the uterine environment can have effects on offspring bone architecture and integrity that persist into adulthood; however, the biochemical and molecular mechanisms remain unknown. Myostatin is a negative regulator of muscle mass. Parental myostatin deficiency (Mstn) increases muscle mass in wild-type offspring, suggesting an intrauterine programming effect.

Osteoblast Malfunction Caused by Cell Stress Response to Procollagen Misfolding in α2(I)-G610C Mouse Model of Osteogenesis Imperfecta.

Glycine (Gly) substitutions in collagen Gly-X-Y repeats disrupt folding of type I procollagen triple helix and cause severe bone fragility and malformations (osteogenesis imperfecta [OI]). However, these mutations do not elicit the expected endoplasmic reticulum (ER) stress response, in contrast to other protein-folding diseases. Thus, it has remained unclear whether cell stress and osteoblast malfunction contribute to the bone pathology caused by Gly substitutions.

Myostatin deficiency partially rescues the bone phenotype of osteogenesis imperfecta model mice.

Unlabelled: Mice with osteogenesis imperfecta (+/oim), a disorder of bone fragility, were bred to mice with muscle over growth to test whether increasing muscle mass genetically would improve bone quality and strength. The results demonstrate that femora from mice carrying both mutations have greater mechanical integrity than their +/oim littermates.

Introduction: Osteogenesis imperfecta is a heritable connective tissue disorder due primarily to mutations in the type I collagen genes resulting in skeletal deformity and fragility.

Normal spinous process metaphyseal-equivalent lucency simulating infant abuse fractures.

We report a normal radiographic finding that may be mistaken for child abuse trauma in the posterior thoracolumbar spinous processes of young infants after the first week of life. A lucency paralleling the posterior margin of the ossified spinous process is equivalent to the metaphyseal lucent bands seen normally after about a week of the child's age at the ends of long tubular bones. A similar lucency is seen just under the growth plate of vertebral bodies at that early age, giving the bone-in-bone appearance.

Hindlimb Skeletal Muscle Function and Skeletal Quality and Strength in +/G610C Mice With and Without Weight-Bearing Exercise.

Osteogenesis imperfecta (OI) is a heterogeneous heritable connective tissue disorder associated with reduced bone mineral density and skeletal fragility. Bone is inherently mechanosensitive, with bone strength being proportional to muscle mass and strength. Physically active healthy children accrue more bone than inactive children.