Cyclin A2 is essential for mouse gonocyte maturation.

In mammals, male gonocytes are derived from primordial germ cells during embryogenesis, enter a period of mitotic proliferation, and then become quiescent until birth. After birth, the gonocytes proliferate and migrate from the center of testicular cord toward the basement membrane to form the pool of spermatogonial stem cells (SSCs) and establish the SSC niche architecture. However, the molecular mechanisms underlying gonocyte proliferation, migration and differentiation are largely unknown.

HDAC inhibitors elicit metabolic reprogramming by targeting super-enhancers in glioblastoma models.

The Warburg effect is a tumor-related phenomenon that could potentially be targeted therapeutically. Here, we showed that glioblastoma (GBM) cultures and patients' tumors harbored super-enhancers in several genes related to the Warburg effect. By conducting a transcriptome analysis followed by ChIP-Seq coupled with a comprehensive metabolite analysis in GBM models, we found that FDA-approved global (panobinostat, vorinostat) and selective (romidepsin) histone deacetylase (HDAC) inhibitors elicited metabolic reprogramming in concert with disruption of several Warburg effect-related super-enhancers.

Metabolic Reprogramming by c-MET Inhibition as a Targetable Vulnerability in Glioblastoma.

The elucidation of better treatments for solid tumors and especially malignant glial tumors is a priority. Better understanding of the molecular underpinnings of treatment response and resistance are critical determinants in the success for this endeavor. Recently, a battery of novel tools have surfaced that allow to interrogate tumor cell metabolism to more precise extent than this was possible in the earlier days.

Variation in accessory mental foramen frequency and number in extant hominoids.

Nerves providing sensation to the lower face and jaw exit the mandibular canal via the mental foramen. In humans, there are many documented occurrences of additional foramina (accessory mental foramina, AMFs) on the lateral mandibular surface that may also contain nervous structures. There are large discrepancies in the literature regarding how often AMFs occur in humans, and investigations of non-human hominoid AMFs are rare.

Novel IDH1-Targeted Glioma Therapies.

Mutations in the isocitrate dehydrogenase (IDH) 1 gene are commonly found in human glioma, with the majority of low-grade gliomas harboring a recurrent point mutation (IDH1 R132H). Mutant IDH reveals an altered enzymatic activity leading to the synthesis of 2-hydroxyglutarate, which has been implicated in epigenetic mechanisms of oncogenesis. Nevertheless, it is unclear exactly how IDH mutations drive glioma initiation and progression, and it is also not clear why tumors with this mutation generally have a better prognosis than IDH wild-type tumors.

MET Inhibition Elicits PGC1α-Dependent Metabolic Reprogramming in Glioblastoma.

The receptor kinase c-MET has emerged as a target for glioblastoma therapy. However, treatment resistance emerges inevitably. Here, we performed global metabolite screening with metabolite set enrichment coupled with transcriptome and gene set enrichment analysis and proteomic screening, and identified substantial reprogramming of tumor metabolism involving oxidative phosphorylation and fatty acid oxidation (FAO) with substantial accumulation of acyl-carnitines accompanied by an increase of PGC1α in response to genetic (shRNA and CRISPR/Cas9) and pharmacologic (crizotinib) inhibition of c-MET.

Activation of LXRβ inhibits tumor respiration and is synthetically lethal with Bcl-xL inhibition.

Liver-X-receptor (LXR) agonists are known to bear anti-tumor activity. However, their efficacy is limited and additional insights regarding the underlying mechanism are necessary. By performing transcriptome analysis coupled with global polar metabolite screening, we show that LXR agonists, LXR623 and GW3965, enhance synergistically the anti-proliferative effect of BH3 mimetics in solid tumor malignancies, which is predominantly mediated by cell death with features of apoptosis and is rescued by exogenous cholesterol.

Activation of LXR Receptors and Inhibition of TRAP1 Causes Synthetic Lethality in Solid Tumors.

Cholesterol is a pivotal factor for cancer cells to entertain their relentless growth. In this case, we provide a novel strategy to inhibit tumor growth by simultaneous activation of liver-X-receptors and interference with Tumor Necrosis Factor Receptor-associated Protein 1 (TRAP1). Informed by a transcriptomic and subsequent gene set enrichment analysis, we demonstrate that inhibition of TRAP1 results in suppression of the cholesterol synthesis pathway in stem-like and established glioblastoma (GBM) cells by destabilizing the transcription factor SREBP2.

Effects of vitamin D3 and its chemical analogs on the growth of Hodgkin's lymphoma, in vitro.

Objective: Vitamin D receptor (VDR) activities have been noted for a number of B cell malignancies which showed varying sensitivities to vitamin D3 (1,25-dihydroxyvitamin D3, VD3, calcitriol) and its synthetic analogs. The objective of this study was to address the potential effects of VD3 and vitamin D3 analogs (VDAs) on the growth of Hodgkin's lymphoma (HL), a malignant pathology of B cell origin, in vitro.

Results: Immunofluorescence staining showed the expression of VDR by primary Hodgkin's (H) and Reed-Sternberg (RS)-HRS-tumor cells in HL histological sections.

The impact of fertilizers on the uptake of manganese in Cherry Belle radish plants: implications for human health.

Miracle-Gro Singles, Miracle-Gro Shake and Feed, and Vigoro fertilizers are associated with net loss/enhancement of Mn, up to an order of magnitude when referenced to controls in soil, radish vegetables, and radish leaves; Mn enhancements are a factor of 4 to 65 below the daily required intake for humans (2-5.5 mg/day). Manganese levels were measured by atomic absorption spectrometry (AAS).

Dual Inhibition of Bcl-2/Bcl-xL and XPO1 is synthetically lethal in glioblastoma model systems.

XPO1 has recently emerged as a viable treatment target for solid malignancies, including glioblastoma (GBM), the most common primary malignant brain tumor in adults. However, given that tumors become commonly resistant to single treatments, the identification of combination therapies is critical. Therefore, we tested the hypothesis that inhibition of anti-apoptotic Bcl-2 family members and XPO1 are synthetically lethal.

Putative Cellular and Molecular Roles of Zika Virus in Fetal and Pediatric Neuropathologies.

Although the World Health Organization declared an end to the recent Zika virus (ZIKV) outbreak and its association with adverse fetal and pediatric outcome, on November 18, 2016, the virus still remains a severe public health threat. Laboratory experiments thus far supported the suspicions that ZIKV is a teratogenic agent. Evidence indicated that ZIKV infection cripples the host cells' innate immune responses, allowing productive replication and potential dissemination of the virus.

Oblique human symphyseal angle is associated with an evolutionary rate-shift early in the hominin clade.

The rate of change in primate mandibular symphyseal angles was modeled with particular aim of locating a rate-shift within the hominin clade. Prior work noted that the human symphyseal angle must have experienced a rapid rate of change in order to assume the modern human form, suggestive of the non-random work of natural selection. This study indicates that the rate of symphyseal evolution rose dramatically between Australopithecus anamensis and Australopithecus afarensis and continued throughout the diversification of the hominin clade.

Mandibular ramus shape variation and ontogeny in Homo sapiens and Homo neanderthalensis.

As the interface between the mandible and cranium, the mandibular ramus is functionally significant and its morphology has been suggested to be informative for taxonomic and phylogenetic analyses. In primates, and particularly in great apes and humans, ramus morphology is highly variable, especially in the shape of the coronoid process and the relationship of the ramus to the alveolar margin. Here we compare ramus shape variation through ontogeny in Homo neanderthalensis to that of modern and fossil Homo sapiens using geometric morphometric analyses of two-dimensional semilandmarks and univariate measurements of ramus angulation and relative coronoid and condyle height.

Caribbean (English-Speaking) Women in the United States: Cooking for Diabetes Prevention and Management.

This study surveyed 152 Caribbean-American women about their acculturation levels; their health behaviors; and their perceptions about a website portal for diabetes prevention and management. Participants followed a study link to documents created via SurveyMonkey. The study link included seven edited videos each fewer than 2 min; the videos included ingredients; preparation/cooking instructions; and plating tips for modifying traditional Caribbean meals for diabetes management and prevention.

Dextran hydrogels by crosslinking with amino acid diamines and their viscoelastic properties.

Amine functionalized polysaccharide hydrogels such as those based on chitosan are widely examined as biomaterials. Here we set out to develop a facile procedure for developing such hydrogels by crosslinking dextran with amino acid diamines. The dextran-amino acid gels were formed by the addition of the amino acid diamines to a dextran and epichlorohydrin solution once it became homogeneous.

An Msh3 ATPase domain mutation has no effect on MMR function.

Objective: To demonstrate that the Msh3 ATPase domain is required for DNA mismatch repair and tumor suppression in a murine model.

Results: The DNA mismatch repair proteins are members of the ABC family of ATPases. ATP binding and hydrolysis regulates their mismatch repair function.

'Irish & Roman Catholic Which Upsets All the People Here': Michael McDonnell and British Colonial Justice in Mandatory Palestine, 1927-1936.

In 1927 Michael McDonnell, a diasporic Irish Catholic, was appointed Mandatory Palestine's Chief Justice, being directed to institute firm British-style legal-judicial foundations for future self-governance. This entailed common, equal status for Arab and Jewish Palestinians, implicitly de-privileging the Jewish National Home. McDonnell was resisted in this by the British Mandate's Anglo-Jewish, pro-Zionist Attorney General, Norman Bentwich.

Insights into the molecular roles of Zika virus in human reproductive complications and congenital neuropathologies.

The recent upsurge in the association of congenital neurological disorders and infection by the Zika virus (ZIKV) has resulted in increased research focus on the biology of this flavivirus. Studies in animal models indicate that ZIKV can breach the placental barrier and selectively infect and deplete neuroprogenitor cells (NPCs) of the developing fetus, resulting in changes of brain structures, reminiscent of human microcephaly. In vitro and ex vivo studies using human cells and tissues showed that human NPCs and placental cells are targeted by ZIKV.

Error in geometric morphometric data collection: Combining data from multiple sources.

Objectives: This study compares two- and three-dimensional morphometric data to determine the extent to which intra- and interobserver and intermethod error influence the outcomes of statistical analyses.

Materials And Methods: Data were collected five times for each method and observer on 14 anthropoid crania using calipers, a MicroScribe, and 3D models created from NextEngine and microCT scans. ANOVA models were used to examine variance in the linear data at the level of genus, species, specimen, observer, method, and trial.