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\"This is the first major museum publication dedicated to New Guinea Highlands art, celebrating its dynamism, innovative forms, and extraordinary use of materials and recognizing generations of Highlands artists. The Jolika Collection represents decades of focused connoisseurship. The Friedes, members of the Fine Arts Museums staff, scholars of Highlands visual culture, and anthropologists from around the globe have contributed their expertise to this book, researching and recording the collection's works so that they can be shared with the public\"-- Provided by publisher.

The prevalence of neurodegenerative diseases such as Parkinson’s disease (PD) and Alzheimer’s disease (AD) in the U.S. is expected to increase as the population ages. Despite significant advancements in neurodegenerative research, the initiating events remain unclear, and no treatments currently exist to stop or reverse disease pathogenesis. Emerging studies highlight the importance of the gut microbiome and gut-brain-axis in the pathogenesis of many human diseases. This narrative review aims to integrate current research investigating how gut microbial dysbiosis may influence the development and progression of AD and PD. First, we provide an overview of the pathological features and disease mechanisms characteristic of AD and PD. Next, we summarize existing research on the microbiome–gut–brain axis and how alterations in gut microbiota composition may influence these neurological diseases. We then focus on specific bacterial taxa identified in fecal samples from AD and PD patients, highlighting differences from healthy controls and emphasizing taxa known to produce immunologically relevant metabolites and antigens. Specifically, we examine reductions in short-chain fatty acid (SCFA)-producing bacteria and increases in lipopolysaccharide (LPS)-expressing bacteria that may drive neuroinflammation and contribute to protein misfolding. Finally, this review presents hypothesized mechanisms by which microbial products such as SCFAs and LPS may interact with host physiology to modulate disease pathogenesis. These include pathways involving systemic inflammation, blood–brain barrier permeability, and neural propagation via the vagus nerve or olfactory bulb. Further research is necessary to determine the causes and effects of bacterial level shifts, but understanding the mechanistic roles of these bacterial products in AD or PD pathogenesis could allow for personalized targeted therapies to either slow or potentially reverse the disease process.

Background Partially hydrolyzed cow’s milk protein (PHP) formulas are nutritionally complete and have a high-quality protein composition, and extensive history of safe use. The current study evaluated growth and safety in healthy term infants receiving a new PHP formula with an added prebiotic blend. Methods In this multi-center, double-blind, controlled, parallel, prospective study, healthy term infants were randomized to receive one of two formulas through 365 days of age: previously marketed intact cow’s milk protein formula (Control, n  = 122) or investigational PHP formula (INV-PHP, n  = 122). Both formulas had an added prebiotic blend of polydextrose (PDX) and galactooligosaccharides (GOS) (1:1, 4 g/L). The primary outcome was rate of weight gain (g/day) from 14 to 120 days of age. To establish equivalence between study formulas, the 90% two-sided confidence interval (CI) of the mean group difference in body weight growth rate from 14 to 120 days of age needed to be contained within a predefined equivalence interval (± 3 g/day). Growth rates through Day 120 and achieved anthropometrics through Day 365 were analyzed by ANOVA. Parent-reported tolerance outcomes were also collected. Medically confirmed adverse events were collected throughout the study period. Results Of 244 infants enrolled and randomized (Control, n  = 122; INV-PHP, n  = 122); 175 completed study feeding through Day 120 (Control, n  = 91; INV-PHP, n  = 84). Equivalence in rate of weight gain from 14 to 120 days of age was demonstrated with the difference in means of 0.5 g/day and 90% CI [− 1.10, 2.08 g/day] within the predefined equivalence interval (± 3 g/day). Mean achieved weight remained between 25th -75th reference percentiles of the WHO growth standard through Day 180 by sex and subsequently tracked between 50th -90th percentiles through Day 365. Formula acceptance and tolerance were good. Stool consistency remained soft in both groups throughout the study. No significant group differences in mean fussiness and gassiness scores, or medically confirmed adverse events were detected. A total of 159 participants completed the Day 365 visit (Control, n  = 82; INV-PHP, n  = 77). Conclusions Overall, partially hydrolyzed cow’s milk protein infant formula with an added prebiotic was safe, well-tolerated, and associated with adequate growth for healthy term infants receiving formula through one year of age. Trial registration ClinicalTrials.gov, ClinicalTrials.gov Identifier NCT05047978. Registered 28 August 2021, https://clinicaltrials.gov/study/NCT05047978.

Organisms require faithful DNA replication to avoid deleterious mutations. In yeast, replicative leading- and lagging-strand DNA polymerases (Pols ε and δ, respectively) have intrinsic proofreading exonucleases that cooperate with each other and mismatch repair to limit spontaneous mutation to less than 1 per genome per cell division. The relationship of these pathways in mammals and their functions in vivo are unknown. Here we show that mouse Pol ε and δ proofreading suppress discrete mutator and cancer phenotypes. We found that inactivation of Pol ε proofreading elevates base-substitution mutations and accelerates a unique spectrum of spontaneous cancers; the types of tumors are entirely different from those triggered by loss of Pol δ proofreading. Intercrosses of Pol ε-, Pol δ-, and mismatch repair-mutant mice show that Pol ε and δ proofreading act in parallel pathways to prevent spontaneous mutation and cancer. These findings distinguish Pol ε and δ functions in vivo and reveal tissue-specific requirements for DNA replication fidelity.

Advancements in electrode technologies to both stimulate and record the central nervous system’s electrical activities are enabling significant improvements in both the understanding and treatment of different neurological diseases. However, the current neural recording and stimulating electrodes are metallic, requiring invasive and damaging methods to interface with neural tissue. These electrodes may also degrade, resulting in additional invasive procedures. Furthermore, metal electrodes may cause nerve damage due to their inherent rigidity. This paper demonstrates that novel electrically conductive organic fibers (ECFs) can be used for direct nerve stimulation. The ECFs were prepared using a standard polyester material as the structural base, with a carbon nanotube ink applied to the surface as the electrical conductor. We report on three experiments: the first one to characterize the conductive properties of the ECFs; the second one to investigate the fiber cytotoxic properties in vitro; and the third one to demonstrate the utility of the ECF for direct nerve stimulation in an in vivo rodent model.

Renal-cell carcinoma (RCC) is a heterogeneous disease consisting of several subtypes based on specific genomic profiles and histological and clinical characteristics. The subtype with the highest prevalence is clear-cell RCC (ccRCC), next is papillary RCC (pRCC), and then chromophobe RCC (chRCC). The ccRCC cell lines are further subdivided into prognostic expression-based subtypes ccA or ccB. This heterogeneity necessitates the development, availability, and utilization of cell line models with the correct disease phenotypic characteristics for RCC research. In this study, we focused on characterizing proteomic differences between the Caki-1 and Caki-2 cell lines that are commonly used in ccRCC research. Both cells are primarily defined as human ccRCC cell lines. Caki-1 cell lines are metastatic, harboring wild-type VHL, whereas Caki-2 are considered as the primary ccRCC cell lines expressing wild-type von Hippel–Lindau protein (pVHL). Here, we performed a comprehensive comparative proteomic analysis of Caki-1 and Caki-2 cells using tandem mass-tag reagents together with liquid chromatography mass spectrometry (LC/MS) for the identification and quantitation of proteins in the two cell lines. Differential regulation of a subset of the proteins identified was validated using orthogonal methods including western blot, q-PCR, and immunofluorescence assays. Integrative bioinformatic analysis identifies the activation/inhibition of specific molecular pathways, upstream regulators, and causal networks that are uniquely regulated and associated with the two cell lines and RCC subtypes, and potentially the disease stage. Altogether, we have identified multiple molecular pathways, including NRF2 signaling, which is the most significantly activated pathway in Caki-2 versus Caki-1 cells. Some of the differentially regulated molecules and signaling pathways could serve as potential diagnostic and prognostic biomarkers and therapeutic targets amongst ccRCC subtypes.

Mutations are a hallmark of cancer. Normal cells minimize spontaneous mutations through the combined actions of polymerase base selectivity, 3′ → 5′ exonucleolytic proofreading, mismatch correction, and DNA damage repair. To determine the consequences of defective proofreading in mammals, we created mice with a point mutation (D400A) in the proofreading domain of DNA polymerase δ (polδ, encoded by the Pold1 gene). We show that this mutation inactivates the 3′ → 5′ exonuclease of polδ and causes a mutator and cancer phenotype in a recessive manner. By 18 months of age, 94% of homozygous Pold1 D400A/D400A mice developed cancer and died (median survival = 10 months). In contrast, only 3–4% of Pold1 +/D400A and Pold1 +/+ mice developed cancer in this time frame. Of the 66 tumors arising in 49 Pold1 D400A/D400A mice, 40 were epithelial in origin (carcinomas), 24 were mesenchymal (lymphomas and sarcomas), and two were composite (teratomas); one-third of these animals developed tumors in more than one tissue. Skin squamous cell carcinoma was the most common tumor type, occurring in 60% of all Pold1 D400A/D400A mice and in 90% of those surviving beyond 8 months of age. These data show that polδ proofreading suppresses spontaneous tumor development and strongly suggest that unrepaired DNA polymerase errors contribute to carcinogenesis. Mice deficient in polδ proofreading provide a tractable model to study mechanisms of epithelial tumorigenesis initiated by a mutator phenotype.

Intrapleural pressure during a forced vital capacity (VC) maneuver is often in excess of that required to generate maximal expiratory airflow. This excess pressure compresses alveolar gas (i.e., thoracic gas compression [TGC]), resulting in underestimated forced expiratory flows (FEFs) at a given lung volume. It is unknown if TGC is influenced by sex; however, because men have larger lungs and stronger respiratory muscles, we hypothesized that men would have greater TGC. We examined TGC across the “effort‐dependent” region of VC in healthy young men (n = 11) and women (n = 12). Subjects performed VC maneuvers at varying efforts while airflow, volume, and esophageal pressure (POES) were measured. Quasistatic expiratory deflation curves were used to obtain lung recoil (PLUNG) and alveolar pressures (i.e., PALV = POES–PLUNG). The raw maximal expiratory flow–volume (MEFVraw) curve was obtained from the “maximum effort” VC maneuver. The TGC‐corrected curve was obtained by constructing a “maximal perimeter” curve from all VC efforts (MEFVcorr). TGC was examined via differences between curves in FEFs (∆FEF), area under the expiratory curves (∆AEX), and estimated compressed gas volume (∆VGC) across the VC range. Men displayed greater total ∆AEX (5.4 ± 2.0 vs. 2.0 ± 1.5 L2·s−1; p < .001). ∆FEF was greater in men at 25% of exhaled volume only (p < .05), whereas ∆VGC was systematically greater in men across the entire VC (main effect; p < .05). PALV was also greater in men throughout forced expiration (p < .01). Taken together, these findings demonstrate that men display more TGC, occurring early in forced expiration, likely due to greater expiratory pressures throughout the forced VC maneuver. We sought to examine whether sex influences the degree to which thoracic gas compression (TGC) underestimates forced expiratory flows at a given lung volume during forced expiration. Men displayed greater TGC than women, particularly at 25% of the forced expired volume. This greater TGC was likely due to greater expiratory pressures generated by men throughout the maneuver. Failure to appropriately account for TGC results in a greater underestimation of expiratory airflow in men, primarily during the early phase of forced expiration.

Chromosomal abnormalities are commonly found in bronchogenic carcinoma cells, but the molecular causes of chromosomal instability (CIN) and their relationship to cigarette smoke has not been defined. Because the Fanconi anaemia (FA)/BRCA pathway is essential for maintenance of chromosomal stability, we tested the hypothesis that cigarette smoke suppresses that activity of this pathway. Here, we show that cigarette smoke condensate (CSC) inhibited translation of FANCD2 mRNA (but not FANCC or FANCG ) in normal airway epithelial cells and that this suppression of FANCD2 expression was sufficient to induce both genetic instability and programmed cell death in the exposed cell population. Cigarette smoke condensate also suppressed FANCD2 function and induced CIN in bronchogenic carcinoma cells, but these cells were resistant to CSC-induced apoptosis relative to normal airway epithelial cells. We, therefore, suggest that CSC exerts pressure on airway epithelial cells that results in selection and emergence of genetically unstable somatic mutant clones that may have lost the capacity to effectively execute an apoptotic programme. Carcinogen-mediated suppression of FANCD2 gene expression provides a plausible molecular mechanism for CIN in bronchogenic carcinogenesis.