Cyclin-dependent kinase-dependent phosphorylation of Lif1 and Sae2 controls imprecise nonhomologous end joining accompanied by double-strand break resection

DNA double-strand breaks (DSBs) are repaired by two distinct pathways, homologous recombination (HR) and nonhomologous end joining (NHEJ). NHEJ includes two pathways, that is, precise and imprecise end joining. We found that Lif1, a component of the DNA ligase IV complex in Saccharomyces cerevisiae, was phosphorylated by cyclin-dependent kinase (CDK) at Ser261 during the S to G2 phase but not during G1 phase. This phosphorylation was required for efficient NHEJ in G2/M cells, rather than in G1 cells. It also promotes the stable binding of Lif1 protein to DSBs, specifically in G2/M-arrested cells, which shows the resection of DSB ends. Thus, Lif1 phosphorylation plays a critical role in a certain type of imprecise NHEJ accompanied by DSB end resection and micro-homology. Lif1 phosphorylation at Ser261 is probably involved in micro-homology-dependent end joining associated with producing single-stranded DSB ends that are formed by Sae2 as early intermediates in the HR pathway. CDK-dependent modification of the NHEJ pathway might make DSB ends compatible for NHEJ and thus prevent competition between HR and NHEJ in hierarchy on the choice of DSB repair pathways.     

The psychological profile and affective response of women diagnosed with unexplained infertility undergoing in vitro fertilization

It has been hypothesized that unexplained infertility may be related to specific personality and coping styles. We studied two groups of women with explained infertility (EIF, n?=?63) and unexplained infertility (UIF, n?=?42) undergoing an in vitro fertilization (IVF) cycle. Women completed personality and coping style questionnaires prior to the onset of the cycle, and state depression and anxiety scales before and at two additional time points during the cycle. Almost no in-between group differences were found at any of the measured time points in regards to the Minnesota Multiphasic Personality Inventory-2 validity and clinical scales, Illness Cognitions and Life Orientation Test, or for the situational measures. The few differences found suggest a more adaptive, better coping, and functioning defensive system in women with EIF. In conclusion, we did not find any clinically significant personality differences or differences in depression or anxiety levels between women with EIF and UIF during an IVF cycle. Minor differences found are probably a reaction to the ambiguous medical situation with its uncertain prognosis, amplifying certain traits which are not specific to one psychological structure but rather to the common experience shared by the group. The results of this study do not support the possibility that personality traits are involved in the pathophysiology of unexplained infertility.     

Identification of proteasome components required for apical localization of Chaoptin using functional genomics

Abstract: the distinct localization of membrane proteins with regard to cell polarity is crucial for the structure and function of various organs in multicellular organisms. However, the molecules and mechanisms that regulate protein localization to particular subcellular domains are still largely unknown. To identify the genes involved in regulation of protein localization, the authors performed a large-scale screen using a Drosophila RNA interference (RNAi) library, by which Drosophila genes could be knocked down in a tissue- and stage-specific manner. Drosophila photoreceptor cells have a morphologically distinct apicobasal polarity, along which Chaoptin (Chp), a glycosylphosphatidylinositol (GPI)-anchored membrane protein, and the Na (+) , K(+) -ATPase are localized to the apical and basolateral domains, respectively. By examining the subcellular localization of these proteins, the authors identified 106 genes whose knockdown resulted in mislocalization of Chp and Na(+) , K(+) -ATPase. Gene ontology analysis revealed that the knockdown of proteasome components resulted in mislocalization of Chp to the basolateral plasma membrane. These results suggest that the proteasome is involved, directly or indirectly, in selective localization of Chp to the apical plasma membrane of Drosophila photoreceptor cells.     

Castleman’s disease along the left tracheobronchial tree with a difficult preoperative diagnosis

A 39-year-old man was referred to our hospital because of an asymptomatic middle mediastinal tumor. A preliminary histological diagnosis of the tumor by bronchoscopy was difficult to obtain because the tumor was located along the left tracheobronchial tree, which is difficult to approach. The tumor was resected through a right anteroaxillary thoracotomy without any major complications, and histopathological examination revealed that the lesion was Castleman’s disease, hyaline-vascular type. Radiological findings of the lesion were typical; however, the rarity of the tumor made the imaging diagnosis difficult. If a lesion is located along the tracheobronchial tree, Castleman’s disease should be considered in the differential diagnosis.     

Delayed Visual Recovery from Severe Ethambutol Optic Neuropathy in Two Patients with Atypical Mycobacterium Infection

Two patients with atypical mycobacterium infection developed severe ethambutol optic neuropathy for a long period of time followed by good recovery. A 74-year-old female (Case 1) developed reduced visual acuity of 20/200 OD and 20/400 OS after oral administration of ethambutol for 14 months, and ethambutol was discontinued. A 63-year-old female (Case 2) developed a visual acuity of CF10' OD and 20/400 OS after oral administration of ethambutol for 10 months, and ethambutol was discontinued. Cases 1 and 2 had anemia after having undergone gastrectomy 10 years or 5 years earlier, respectively, and both had rheumatoid arthritis. At the onset of ethambutol optic neuropathy, both patients developed severe bilateral visual loss with bitemporal hemianopia-like visual field disturbance. However, Cases 1 and 2 did not show disc pallor nor nerve fiber layer defect (NFLD) at any time during the follow-up period, and had good recovery in visual function at 18 months or 19 months after the onset of optic neuropathy, respectively. In patients with severe ethambutol optic neuropathy, as long as disc pallor and NFLD are not observed, good visual recovery may be expected even if severe visual loss persists for a long period of time.     

Cyclosporine A for chemotherapy-resistant subcutaneous panniculitis-like T cell lymphoma with hemophagocytic syndrome

Subcutaneous panniculitis-like T cell lymphoma (SPTL) is a rare subtype of non-Hodgkin lymphoma for which a definitive therapeutic strategy has not been established yet. We report a case of chemotherapy-resistant SPTL with hemophagocytic syndrome (HPS) which was successfully treated with cyclosporine A (CsA) plus methylprednisolone (mPSL), and also reviewed 11 SPTL cases treated with CsA, previously reported in the literature. Our patient was a 38-year-old female with SPTL. The disease progressed despite conventional chemotherapy using cytotoxic agents including alkylators, anthracyclins or purine analogues, and, after 2 months of chemotherapy, was eventually complicated by HPS and disseminated intravascular coagulation (DIC). CsA (4 mg/kg/day) plus mPSL treatment dramatically improved HPS with DIC, reduced subcutaneous tumors within 2 weeks, and finally induced complete remission (CR) after 3 months. Currently, the patient has maintained CR while being treated with CsA for 12 months. In addition to our case, 9 of 11 SPTL cases were successfully treated with CsA, and 8 were induced to CR. Time to first response to CsA was within 2 weeks in most cases, regardless of prior treatment or the co-occurrence of HPS. Our case and this first comprehensive review on CsA for SPTL suggest that CsA may constitute a candidate treatment strategy for SPTL.