Distinctive Higgs signals of a type II 2HDM at the LHC

We perform a numerical analysis of Higgs-to-Higgs decays within a type II two-Higgs-doublet model (2HDM), highlighting several channels that cannot occur in its supersymmetric version, thereby allowing one to possibly distinguish between these two scenarios. Our results are compliant with all available experimental bounds from both direct and indirect Higgs searches and with theoretical constraints from vacuum stability and perturbative unitarity

Mild treadmill exercise inhibits cartilage degeneration via macrophages in an osteoarthritis mouse model

Objective: We previously reported how treadmill exercise can suppress cartilage degeneration. Here, we examined the changes in macrophage dynamics in knee osteoarthritis (OA) during treadmill exercise and the effect of macrophage depletion. Design: OA mouse model, generated via anterior cruciate ligament transection (ACLT), was subjected to treadmill exercise of different intensities to investigate the effects on cartilage and synovium. In addition, clodronate liposomes, which deplete macrophages, were injected intra-articularly into the joint to examine the role of macrophages during treadmill exercise. Results: Cartilage degeneration was delayed by mild exercise, and concomitantly, an increase in anti-inflammatory factors in the synovium was observed, with a decrease in the M1 and increase in M2 macrophage ratio. On the contrary, high-intensity exercise led to the progress of cartilage degeneration and was associated with an increase in the M1 and a decrease in the M2 macrophage ratio. The clodronate liposome-induced reduction of synovial macrophages delayed cartilage degeneration. This phenotype was reversed by simultaneous treadmill exercise. Conclusions: Treadmill exercise, especially at high intensity, was detrimental to articular cartilage, whereas mild exercise reduced cartilage degeneration. Moreover, M2 macrophage response appeared necessary for the chondroprotective effect of treadmill exercise. This study indicates the importance of a more comprehensive analysis of the effects of treadmill exercise, not limited to the mechanical stress added directly to cartilage. Hence, our findings might help determine the type and intensity of prescribed exercise therapy for patients with knee OA

Effect of Various Types of Muscle Contraction with Different Running Conditions on Mouse Humerus Morphology

How various types of muscle contraction during exercises affect bone formation remains unclear. This study aimed to determine how exercises with different muscle contraction types affect bone morphology. In total, 20 mice were used and divided into four groups: Control, Level, Down Slow, and Down. Different types of muscle contraction were induced by changing the running angle of the treadmill. After the intervention, micro-computed tomography (Micro-CT), tartrate-resistant acid phosphatase/alkaline phosphatase (ALP) staining, and immunohistochemical staining were used to analyze the humerus head, tendon-to-bone attachment, and humerus diaphyseal region. Micro-CT found that the volume ratio of the humeral head, the volume of the tendon-to-bone attachment region, and the area of the humeral diaphyseal region increased in the Down group. However, no difference was detected in bone morphology between the Level and Down Slow groups. In addition, histology showed activation of ALP in the subarticular subchondral region in the Down Slow and Down groups and the fibrocartilage region in the tendon-to-bone attachment. Moreover, Osterix increased predominantly in the Down Slow and Down groups.Overall bone morphological changes in the humerus occur only when overuse is added to EC-dominant activity. Furthermore, different type of muscle contractile activities might promote bone formation in a site-specific manner

Treadmill Exercise after Controlled Abnormal Joint Movement Inhibits Cartilage Degeneration and Synovitis

Cartilage degeneration is the main pathological component of knee osteoarthritis (OA), but no effective treatment for its control exists. Although exercise can inhibit OA, the abnormal joint movement with knee OA must be managed to perform exercise. Our aims were to determine how controlling abnormal joint movement and treadmill exercise can suppress cartilage degeneration, to analyze the tissues surrounding articular cartilage, and to clarify the effect of treatment. Twelve-week-old ICR mice (n = 24) underwent anterior cruciate ligament transection (ACL-T) surgery on their right knees and were divided into three groups as follows: ACL-T, animals in the walking group subjected to ACL-T; controlled abnormal joint movement (CAJM), and CAJM with exercise (CAJM + Ex) (n = 8/group). Walking-group animals were subjected to treadmill exercise 6 weeks after surgery, including walking for 18 m/min, 30 min/day, 3 days/week for 8 weeks. Safranin-O staining, hematoxylin-eosin staining, and immunohistochemical staining were performed. The OARSI (Osteoarthritis research Society international) score was lower in the CAJM group than in the ACL-T group and was even lower in the CAJM + Ex group. The CAJM group had a lower meniscal injury score than the ACL-T group, and the CAJM + Ex group demonstrated a less severe synovitis than the ACL-T and CAJM groups. The observed difference in the perichondrium tissue damage score depending on the intervention method suggests different therapeutic effects, that normalizing joint motion can solve local problems in the knee joint, and that the anti-inflammatory effect of treadmill exercise can suppress cartilage degeneration

Sarcomatoid malignant pleural mesothelioma associated with anti-Ma2-related paraneoplastic neurological syndrome: A case report

Paraneoplastic neurological syndrome (PNS) is rarely associated with malignant pleural mesothelioma (MPM). We report the first case of sarcomatoid mesothelioma in a 63-year-old female diagnosed with cerebellar degeneration in January 2018. Systemic examination showed right pleura thickening. The pleural biopsy of the mass revealed a sarcomatoid MPM cT3N0M0. In February 2018, anti-Ma2 antibody positivity indicated PNS complicated with MPM. First, cisplatin (75 mg/m2) + pemetrexed (500 mg/m2) chemotherapy was given. For PNS, steroid pulse therapy and high-dose immunoglobulin therapy were administered. MPM may cause anti-Ma2 antibody-related PNS. Early diagnosis and starting anticancer treatment and immunotherapy are critical

Dysfunction of the proteoglycan Tsukushi causes hydrocephalus through altered neurogenesis in the subventricular zone in mice

The lateral ventricle (LV) is flanked by the subventricular zone (SVZ), a neural stem cell (NSC) niche rich in extrinsic growth factors regulating NSC maintenance, proliferation, and neuronal differentiation. Dysregulation of the SVZ niche causes LV expansion, a condition known as hydrocephalus; however, the underlying pathological mechanisms are unclear. We show that deficiency of the proteoglycan Tsukushi (TSK) in ependymal cells at the LV surface and in the cerebrospinal fluid results in hydrocephalus with neurodevelopmental disorder-like symptoms in mice. These symptoms are accompanied by altered differentiation and survival of the NSC lineage, disrupted ependymal structure, and dysregulated Wnt signaling. Multiple TSK variants found in patients with hydrocephalus exhibit reduced physiological activity in mice in vivo and in vitro. Administration of wild-type TSK protein or Wnt antagonists, but not of hydrocephalus-related TSK variants, in the LV of TSK knockout mice prevented hydrocephalus and preserved SVZ neurogenesis. These observations suggest that TSK plays a crucial role as a niche molecule modulating the fate of SVZ NSCs and point to TSK as a candidate for the diagnosis and therapy of hydrocephalus

IMP dehydrogenase-2 drives aberrant nucleolar activity and promotes tumorigenesis in glioblastoma

In many cancers, high proliferation rates correlate with elevation of rRNA and tRNA levels, and nucleolar hypertrophy. However, the underlying mechanisms linking increased nucleolar transcription and tumorigenesis are only minimally understood. Here we show that IMP dehydrogenase-2 (IMPDH2), the rate-limiting enzyme for de novo guanine nucleotide biosynthesis, is overexpressed in the highly lethal brain cancer glioblastoma. This leads to increased rRNA and tRNA synthesis, stabilization of the nucleolar GTP-binding protein nucleostemin, and enlarged, malformed nucleoli. Pharmacological or genetic inactivation of IMPDH2 in glioblastoma reverses these effects and inhibits cell proliferation, whereas untransformed glia cells are unaffected by similar IMPDH2 perturbations. Impairment of IMPDH2 activity triggers nucleolar stress and growth arrest of glioblastoma cells even in the absence of functional p53. Our results reveal that upregulation of IMPDH2 is a prerequisite for the occurance of aberrant nucleolar function and increased anabolic processes in glioblastoma, which constitutes a primary event in gliomagenesis