Stochastic ERK activation induced by noise and cell-to-cell propagation regulates cell density-dependent proliferation.

The extracellular signal-regulated kinase (ERK) plays a central role in the signaling cascades of cell growth. Here, we show that stochastic ERK activity pulses regulate cell proliferation rates in a cell density-dependent manner. A fluorescence resonance energy transfer (FRET) biosensor revealed that stochastic ERK activity pulses fired spontaneously or propagated from adjacent cells. Frequency, but not amplitude, of ERK activity pulses exhibited a bell-shaped response to the cell density and correlated with cell proliferation rates. Consistently, synthetic ERK activity pulses generated by a light-switchable CRaf protein accelerated cell proliferation. A mathematical model clarified that 80% and 20% of ERK activity pulses are generated by the noise and cell-to-cell propagation, respectively. Finally, RNA sequencing analysis of cells subjected to the synthetic ERK activity pulses suggested the involvement of serum responsive factor (SRF) transcription factors in the gene expression driven by the ERK activity pulses.

Disparate responses to salinity across species and organizational levels in anchialine shrimps.

Environmentally induced plasticity in gene expression is one of the underlying mechanisms of adaptation to habitats with variable environments. For example, euryhaline crustaceans show predictable changes in the expression of ion-transporter genes during salinity transfers, although studies have typically been limited to specific genes, taxa and ecosystems of interest. Here, we investigated responses to salinity change at multiple organizational levels in five species of shrimp representing at least three independent invasions of the anchialine ecosystem, defined as habitats with marine and freshwater influences with spatial and temporal fluctuations in salinity. Although all five species were generally strong osmoregulators, salinity-induced changes in gill physiology and gene expression were highly species specific. While some species exhibited patterns similar to those of previously studied euryhaline crustaceans, instances of distinct and atypical patterns were recovered from closely related species. Species-specific patterns were found when examining: (1) numbers and identities of differentially expressed genes, (2) salinity-induced expression of genes predicted a priori to play a role in osmoregulation, and (3) salinity-induced expression of orthologs shared among all species. Notably, ion transport genes were unchanged in the atyid Halocaridina rubra while genes normally associated with vision and light perception were among those most highly upregulated. Potential reasons for species-specific patterns are discussed, including variation among anchialine habitats in salinity regimes and divergent evolution in anchialine taxa. Underexplored mechanisms of osmoregulation in crustaceans revealed here by the application of transcriptomic approaches to ecologically and taxonomically understudied systems are also explored.

Four Aromatic Sulfates with an Inhibitory Effect against HCV NS3 Helicase from the Crinoid Alloeocomatella polycladia.

Bioassay-guided separation of a lipophilic extract of the crinoid Alloeocomatella polycladia, inhibiting the activity of HCV NS3 helicase, yielded two groups of molecules: cholesterol sulfate and four new aromatic sulfates 1-4. The structures of the aromatics were elucidated by spectroscopic analysis in addition to theoretical studies. The aromatic sulfates 1-4 showed moderate inhibition against NS3 helicase with IC50 values of 71, 95, 7, and 5 µM, respectively.

[A Case of Perforative Peritonitis Due to Intestinal Metastasis from Lung Cancer].

We here describe a case of an acute peritonitis due to perforation of a small intestine tumor metastasized from a lung cancer. A 66-year-old man who had undergone a bladder cancer procedure 2 years ago and was hospitalized for the second operation, complained sudden abdominal pain. An enhanced abdominal CTrevealed a small amount of free gas and ascites in the abdominal cavity. On the same day, emergency exploratory surgery was performed with the diagnosis of perforative peritonitis. A laparotomy revealed a jejunal tumor with perforation 40 cm distal from the Treitz ligament. After surgery, the patient confessed that he had got a notice of the recurrence of lung cancer which had been treated 9 years ago. The pathological result indicated the lesion was metastasis from lung cancer. Although small intestinal metastatic tumor from lung cancer is rare, it should be considered when acute abdomen is observed.

Sudden hypoxemia after uneventful laparoscopic cholecystectomy: another form of SAM presentation.

BACKGROUND: Perioperative dynamic left ventricular outflow obstruction associated with systolic anterior motion of the mitral valve is well recognized as a cause for unexplained sudden hypotension in perioperative settings, even without underlying heart diseases such as hypertrophic obstructive cardiomyopathy. We treated a patient who experienced sudden hypoxemia without severe hypotension during emergence from anesthesia after an uneventful laparoscopic cholecystectomy. CASE PRESENTATION: A 65-year-old female patient with a history of hypertension presented a sudden decrease in oxygen saturation to 80% after an uneventful cholecystectomy. Although a portable chest radiograph showed bilateral hilar pulmonary infiltrates consistent with pulmonary edema, we explored the underlying cause, i.e., systolic anterior motion of the mitral valve and left ventricular outflow tract obstruction with bedside transthoracic echocardiography. We speculate that dynamic mitral regurgitation resulted in pulmonary edema and, thereby, hypoxemia in this case without severe hypotension. CONCLUSIONS: Careful bedside examination with transthoracic echocardiography was useful in making diagnosis and in guiding appropriate therapy for this patient. Clinicians should be aware that systolic anterior motion of the mitral valve may present as unexplained sudden hypoxemia in the perioperative setting.

D-dimer testing cannot rule out thromboembolism after major lower extremity arthroplasties and thromboprophylaxis treatment.

PURPOSE: Our previous study showed, for the first time, that a guideline-recommended thromboprophylactic strategy reduced the prevalence of venous thromboembolism (VTE) including venous thromboembolism and pulmonary embolism after arthroplasties of the major lower extremities, such as total hip arthroplasty (THA) or total or partial knee arthroplasty (TPKA), to 4.4 %. In this retrospective study, we examined the diagnostic value of D-dimer for VTE and try to confirm the low prevalence of VTE after THA or TPKA. METHODS: This was a retrospective study including 380 procedures of 361 patients who underwent elective 129 TPKA or 251 THA, as well as multidetector computed tomography (MDCT) on postoperative day 7 with D-timer testing to screen for VTE. In 303 of 380 procedures, D-timer testing was performed on the same day as MDCT. The antithrombotic prophylaxes included medical and mechanical therapy and early ambulation. RESULTS: The prevalence of VTE was 4.5 % (17 cases) (95 % confidence interval 2.4-6.6 %). The D-dimer level was significantly greater in patients with VTE than in those without (13.4 ± 11.1 vs 10.1 ± 6.5 µg/mL). At the lowest cut-off value of 4.0 µg/mL, D-dimer testing ruled out VTE in only 26 of 303 cases with 1 (6 %) false negative result. CONCLUSIONS: The low incidence of postoperative VTE with the strict anticoagulation strategy was confirmed in this validation study. D-dimer testing is not useful for excluding VTE postoperatively in patients who undergo THA or TPKA.

The incidence of pulmonary embolism and deep vein thrombosis and their predictive risk factors after lower extremity arthroplasty: a retrospective analysis based on diagnosis using multidetector CT.

PURPOSE: The true incidence of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE) events, and the predictive risk factors are not well-defined in patients who undergo major lower extremity arthroplasty such as total hip arthroplasty (THA) or total or partial knee arthroplasty (TPKA). Using multidetector computed tomography (MDCT), pulmonary angiography (CTA), and MDCT venography (CTV), we investigated the prevalence of VTE and its predictive risk factors in patients for whom the guideline recommends prophylaxis. METHODS: The electronic records of patients who underwent elective THA or TPKA at our institution from April 2010 through July 2013 were surveyed. We examined a total of 1,163 patient records for 986 patients who had undergone MDCT seven days after THA or TPKA. RESULTS: No PE-related deaths occurred in this study, though arterial embolization was needed for major bleeding in two cases. CTA-CTV revealed VTE in 51 (4.4 %) patients, PE in 20 (1.7 %), and DVT in 43 (3.3 %). Five of 51 patients had symptoms suggestive of DVT. In the logistic regression model, the type of surgery (TPKA > THA), patient age, and body mass index (BMI) were identified as predictive risk factors for VTE. CONCLUSIONS: This observational study showed that the overall incidence of VTE after THA and TPKA is 4.4 % in patients receiving recommended antithrombotic prophylaxis. TPKA is associated with a higher incidence of VTE than of THA, and greater BMI and older patient age are also independent risk factors.

[Repeated Insertion of Self-Expandable Metallic Stents as a Palliative Therapy for Unresectable Colorectal Cancer].

A 62-year-old man was admitted to our hospital for malignant rectal stricture due to metastatic rectal cancer. He underwent placement of a self-expandable metallic stent (SEMS). After the administration of 5 courses of FOLFOX4 with bevacizumab, chemotherapy-induced tumor shrinkage led to migration of the SEMS, which was removed immediately without complication. After 10 courses of chemotherapy, he had to discontinue the treatment due to liver failure resulting from tumor progression. Another SEMS was successfully inserted for the progression of rectal stenosis. The patient's QOL was maintained to the end with the SEMS. This case suggests that although it is essential to pay attention to possible complications, SEMS insertion is a very useful procedure for palliative therapy.

[Conversion Therapy of Initially Unresectable Rectal Cancer with Perforation via FOLFOX4 Chemotherapy].

We describe a case of perforated rectal cancer that became curatively resectable after FOLFOX4 chemotherapy. An 81- year-old woman was transferred to our hospital with a diagnosis of bowel perforation. She underwent emergency transverse colostomy, peritoneal lavage, and the insertion of indwelling drainage tubes, because the perforated rectal cancer was considered unresectable. After recuperation, she received chemotherapy consisting of FOLFOX4 and bevacizumab. Owing to a good response to the treatment after 4 months, rectal resection was achieved curatively. Wound dehiscence occurred as a postoperative complication. The patient chose not to receive adjuvant chemotherapy. Currently, she has been alive for more than 1 year 3 months after resection without recurrence.

Taking their breath away: metabolic responses to low-oxygen levels in anchialine shrimps (Crustacea: Atyidae and Alpheidae).

Crustaceans generally act as oxy-regulators, maintaining constant oxygen uptake as oxygen partial pressures decrease, but when a critical low level is reached, ventilation and aerobic metabolism shut down. Cave-adapted animals, including crustaceans, often show a reduced metabolic rate possibly owing in part to the hypoxic nature of such environments. However, metabolic rates have not been thoroughly explored in crustaceans from anchialine habitats (coastal ponds and caves), which can experience variable oxygenic regimes. Here, an atypical oxy-conforming pattern of oxygen uptake is reported in the Hawaiian anchialine atyid Halocaridina rubra, along with other unusual metabolic characteristics. Ventilatory rates are near-maximal in normoxia and did not increase appreciably as PO2 declined, resulting in a decline in VO2 during progressive hypoxia. Halocaridina rubra maintained in anoxic waters survived for seven days (the duration of the experiment) with no measureable oxygen uptake, suggesting a reliance on anaerobic metabolism. Supporting this, lactate dehydrogenase activity was high, even in normoxia, and oxygen debts were quickly repaid by an unusually extreme increase in oxygen uptake upon exposure to normoxia. In contrast, four related anchialine shrimp species from the Ryukyu Islands, Japan, exhibited physiological properties consistent with previously studied crustaceans. The unusual respiratory patterns found in H. rubra are discussed in the context of a trade-off in gill morphology for osmoregulatory ion transport vs. diffusion of respiratory gasses. Future focus on anchialine species may offer novel insight into the diversity of metabolic responses to hypoxia and other physiological challenges experienced by crustaceans.

[Long-term control of stage IV breast and gastric cancer with combination therapy of S-1 and paclitaxel].

We here describe a case of Stage IV breast and gastric cancer in which S-1/paclitaxel therapy was effective in maintaining the patient's QOL. A 50-year-old woman visited our hospital with complaints of her right breast tumor and right brachialgia. She was diagnosed with breast cancer with multiple bone metastases including cervical vertebrae. Accordingly, local radiation therapy and tamoxifen(TAM)administration was started immediately. Gastrointestinal endoscopy revealed gastric cancer, but laparotomy disclosed the gastric cancer was unresectable. At that time, the complaints of pain, nausea, and fatigue had increased and S-1/paclitaxel therapy was started immediately. The treatment reduced the size of the lesions in the breast and stomach and improved the QOL without serious adverse events. We have been maintaining partial response(PR)in this patient for 28 months.

[Three cases of endoscopic gastroduodenal stenting for gastric outlet obstruction caused by unresectable gastric cancer].

Gastroduodenal stenting for gastric outlet obstruction (GOO) caused by malignant disease has been covered by health insurance in Japan since April 2010. We have inserted WallFlex™ duodenal stents (WDS) in 3 patients with GOO caused by unresectable advanced gastric cancer. WDS placement was successful with no complications in all cases. Mean treatment time was 44.7 (35-50) minutes, and mean survival time after WDS placement was 34.7 (19-51) days. Oral food intake was improved in all patients but 1. Enteroparalysis due to peritoneal metastasis supposedly voided WDS placement in 1 patient. WDS placement for GOO caused by advanced gastric cancer is expected to be a safe and effective palliative treatment but sometimes yields no benefit in the patient with peritoneal metastasis.

New records of the caridean shrimp genus Processa Leach, 1815 (Crustacea: Decapoda: Processidae) from Japan, with descriptions of two new species.

Three species of the processid shrimp genus Processa Leach, 1815, including two new species, are reported from shallow coastal waters in Okinawa Island, Ryukyu Islands, Japan: P. affinis Hayashi, 1975, P. filipes n. sp. and P. hayashii n. sp. The present specimens of P. affinis represent the rediscovery and range extension of this poorly known species, originally described from Indonesia. Male characteristics of P. affinis are documented for the first time. The two new species are referred to the P. aequimana Paulson, 1875 species group. Processa filipes n. sp. is characteristic in the greatly elongate fifth pereopod and the transverse ridge on thoracic sternite 8 consisting of soft cuticle. Processa hayashii n. sp. is characterized by the presence of a deep concavity on the anterolateral margin of the carapace just inferior to the antennal tooth. The number of species of Processa known from Japanese waters is raised from five to eight.

Diagnostic Ultrasound: On-Site Diagnosis of Type B Aortic Dissection During Cataract Surgery.

We report a case of aortic dissection occurring during cataract surgery under local anesthesia, which was diagnosed on-site by point-of-care ultrasound. Intimal flaps were detected in the abdominal aorta, whereas the parasternal view showed no abnormalities in the aortic root or left ventricular function. According to these ultrasound findings, a Stanford type B aortic dissection was more likely than a type A aortic dissection, and imminent death was unlikely. Therefore, we decided to resume and complete the surgery. Subsequent computed tomography (CT) confirmed the point-of-care diagnosis. The patient was transferred to a tertiary hospital for medical treatment.

A new genus and species of a submarine cave crab of the family Plagusiidae Dana, 1851 (Crustacea: Brachyura: Grapsoidea) from Okinawa Island, Ryukyu Islands, southwestern Japan.

Caligoplagusia okinawa n. gen. & n. sp., assigned to the brachyuran family Plagusiidae Dana, 1851 is described on the basis of a male and a female specimens collected from a semi-submerged marine cave on the limestone shore of Okinawa Island, Ryukyu Islands, southwestern Japan. The new monotypic genus is most similar to Euchirograpsus H. Milne Edwards, 1853 and Miersiograpsus Trkay, 1978 in that the frontal margin lacks a deep sublateral cleft adjacent to the orbit, but differs significantly by its subhexagonal carapace shape, the anterolateral margin of the carapace with three teeth including the external orbital tooth, the anterior margin of ambulatory meri each armed with a row of large teeth, and the greatly reduced eyes. The pale body colour, reduced eyes, the very elongate antennal flagellum, and long ambulatory legs are all typical brachyuran adaptations to living in cave environments. This is the first cave-dwelling species of the family Plagusiidae.

A new species of the genus Trichopagurus de Saint Laurent, 1968 (Crustacea: Decapoda: Anomura: Paguridae) from a semi-submerged marine cave in Okinawa Island, southwestern Japan.

A new hermit crab species of Paguridae, Trichopagurus spinibrachium n. sp., is described on the basis of a single male specimen collected from the anchialine environment of a semi-submerged marine cave in Okinawa Island, Ryukyu Islands, southwestern Japan. It is morphologically similar to T. macrochela Komai & Osawa, 2005 and T. tenuidactylus Komai, 2013, but differs in the shape and armature of the ocular, antennular and antennal peduncles, chelipeds, and ambulatory legs. The new species may be distinguished from all known congeners by the stronger armature of the carpi and meri of both chelipeds. Trichopagurus spinibrachium n. sp. is the third species of the genus recorded from submarine caves, although it may also occur on nearby coral reefs as does T. macrochela and T. trichophthalmus (Forest, 1954).

Asymmetric genetic population structures at the range edges of a mangrove whelk.

Many marine species are distributed across incredibly wide geographical ranges spanning thousands of kilometers often due to movement along prevailing ocean currents. However, data are lacking on genetic connectivity among populations of such widespread species within or among ecoregions, possibly due to the lack of appropriate datasets. In this study, we investigated the genetic structure of populations of the mangrove whelk, Terebralia palustris, using mitochondrial cytochrome oxidase subunit I (COI) sequences. Sequences generated for this study from Okinawa, Japan, were compared to samples from the coast of East Africa analyzed in a previous study. Interestingly, despite considerable distance separating them, the African and Japanese populations share major haplotypes and do not show clear genetic differentiation. At lower latitudes, core African populations exhibited higher genetic diversity than either the more southerly African and Japanese populations. Genetic ß-diversity revealed that the northern edge population in Japan has a greater proportion of ßSNE (the nestedness-resultant component), indicating contemporary migration, whereas the southern edge population in Africa is characterized by a predominant ßSIM (the turnover component), suggesting historical demography. A potential cause of this dissimilarity could be due to the strong Kuroshio Current along the Ryukyu Islands, which may promote larval dispersal. These differing patterns suggest that there may be divergent responses to future climate change at the population level at the periphery of the range of T. palustris.

Novel molecular resources for single-specimen barcoding of enigmatic crustacean y-larvae.

Despite discovery more than 100years ago and documented global occurrence from shallow waters to the deep sea, the life cycle of the enigmatic crustacean y-larvae isincompletely understood and adult forms remain unknown. To date, only 2 of the 17 formally described species, all based on larval stages, have been investigated using an integrative taxonomic approach. This approach provided descriptions of the morphology of the naupliar and cyprid stages, and made use of exuvial voucher material and DNA barcodes. To improve our knowledge about the evolutionary history and ecological importance of y-larvae, we developed a novel protocol that maximises the amount of morpho-ecological and molecular data that can be harvested from single larval specimens. This includes single-specimen DNA barcoding and daily imaging of y-nauplii reared in culture dishes, mounting of the last naupliar exuviae on a slide as a reference voucher, live imaging of the y-cyprid instar that follows, and fixation, DNA extraction, amplification and sequencing of the y-cyprid specimen. Through development and testing of a suite of new primers for both nuclear and mitochondrial protein-coding and ribosomal genes, we showcase how new sequence data can be used to estimate the phylogeny of Facetotecta. We expect that our novel procedure will help to unravel the complex systematics of y-larvae and show how these fascinating larval forms have evolved. Moreover, we posit that our protocols should work on larval specimens from a diverse array of moulting marine invertebrate taxa.

[A case of huge advanced hepatocellular carcinoma resected after hepatic arterial infusion therapy of 5-FU/LV/CDDP].

A 58-year-old man was referred to our hospital for a huge tumor occupying the entire right lobe of the liver. An imaging method revealed a 15 cm-sized hepatocellular carcinoma in the right lobe which extended to the internal segment across the middle hepatic vein. The serum AFP level was 15.3 ng/mL, and the level of protein induced by vitamin K absence or antagonist II was 4,340 mAU/mL. We judged it unresectable, then arterial infusion chemotherapy using 5-fluorouracil, cisplatin, and Leucovorin was performed. After 4 courses, the tumor was markedly reduced to 56 mm. We performed an extended right lobectomy. In the operative finding, although the tumor partially reached the internal segment, the middle hepatic vein was preserved. Nine months after operation, no sign of recurrence was found. It is suggested that hepatic arterial infusion therapy is useful for pre-operative therapy of far-advanced hepatocellular carcinoma as a part of combined modality therapy.

New lithistid sponge of the genus Sollasipelta (Porifera, Demospongiae,Tetractinellida, Neopeltidae) from submarine caves of the Ryukyu Islands,southwestern Japan, with redescription of S. sollasi.

A new species of 'lithistid' (rock sponge) Sollasipelta subterranea sp. nov. is described from near-shore submarine caves of Okinawa and Shimoji Islands, the Ryukyu Islands, southwestern Japan. This new species is characterized by the smooth dentate ectosomal pseudophyllotriaenes, slender choanosomal oxea/style/subtylostyles and two types of amphiasters, one of which is in two size classes. Sollasipelta subterranea sp. nov. is morphologically closest to Sollasipelta sollasi (Lévi & Lévi, 1989), known from the Philippines deep sea, and our examination of the type specimen of S. sollasi revealed that the pseudophyllotriaenes and desmas are substantially different between the two species, and both species possess two types of amphiasters, one of which has two size classes. Sollasipelta cavernicola (Vacelet & Vasseur, 1965) and S. punctata (Lévi & Lévi, 1983) are transferred to the genus Daedalopelta Sollas, 1888, based on possession of one type of amphiastes as microscleres. Sollasipelta mixta (Vacelet, Vasseur and Lévi, 1976) is formally transferred to the genus Neopelta Schmidt, 1880, based on the morphological characters. A key to species of the genus Sollasipelta Van Soest & Hooper, 2020 is also provided. Sollasipelta subterranea sp. nov. represents the first 'lithistid' sponge from submarine caves of the Western Pacific and the first species of sponge inhabiting anchialine cave environments in the Indo-West Pacific. This is also a new record of the family Neopeltidae from Japanese waters.