Evidence from sperm whale clans of symbolic marking in non-human cultures.

Culture, a pillar of the remarkable ecological success of humans, is increasingly recognized as a powerful force structuring nonhuman animal populations. A key gap between these two types of culture is quantitative evidence of symbolic markers-seemingly arbitrary traits that function as reliable indicators of cultural group membership to conspecifics. Using acoustic data collected from 23 Pacific Ocean locations, we provide quantitative evidence that certain sperm whale acoustic signals exhibit spatial patterns consistent with a symbolic marker function. Culture segments sperm whale populations into behaviorally distinct clans, which are defined based on dialects of stereotyped click patterns (codas). We classified 23,429 codas into types using contaminated mixture models and hierarchically clustered coda repertoires into seven clans based on similarities in coda usage; then we evaluated whether coda usage varied with geographic distance within clans or with spatial overlap between clans. Similarities in within-clan usage of both "identity codas" (coda types diagnostic of clan identity) and "nonidentity codas" (coda types used by multiple clans) decrease as space between repertoire recording locations increases. However, between-clan similarity in identity, but not nonidentity, coda usage decreases as clan spatial overlap increases. This matches expectations if sympatry is related to a measurable pressure to diversify to make cultural divisions sharper, thereby providing evidence that identity codas function as symbolic markers of clan identity. Our study provides quantitative evidence of arbitrary traits, resembling human ethnic markers, conveying cultural identity outside of humans, and highlights remarkable similarities in the distributions of human ethnolinguistic groups and sperm whale clans.

Spatially resolved birefringence measurements with a digital micro-mirror device.

We demonstrate a novel technique to measure spatially resolved birefringence structures in an all-digital fashion with a digital micro-mirror device (DMD). The technique exploits the polarization independence of DMDs to apply holographic phase control to orthogonal polarization components and requires only a static linear polarizer as an analyzer for the resulting phase shift polarization measurements. We show the efficacy of this approach by spatially resolving complex polarization structures, including nano-structured metasurfaces, customized liquid crystal devices, as well as chiral L-Alanine and N-Acetyl-L-cystein crystals. Concentration dependent measurements of optical rotation in glucose and fructose solutions are also presented, demonstrating the technique's versatility. Unlike conventional approaches, our technique is calibration free and has no moving parts, offers high frame rates and wavelength independence, and is low cost, making it highly suitable to a range of applications, including pharmaceutical manufacturing, saccharimetry and stress imaging.

A Cytotoxic Bis(1,2,3-triazol-5-ylidene)carbazolide Gold(III) Complex Targets DNA by Partial Intercalation.

The syntheses of bis(triazolium)carbazole precursors and their corresponding coinage metal (Au, Ag) complexes are reported. For alkylated triazolium salts, di- or tetranuclear complexes with bridging ligands were isolated, while the bis(aryl) analogue afforded a bis(carbene) AuI -CNC pincer complex suitable for oxidation to the redox-stable [AuIII (CNC)Cl]+ cation. Although the ligand salt and the [AuIII (CNC)Cl]+ complex were both notably cytotoxic toward the breast cancer cell line MDA-MB-231, the AuIII complex was somewhat more selective. Electrophoresis, viscometry, UV-vis, CD and LD spectroscopy suggest the cytotoxic [AuIII (CNC)Cl]+ complex behaves as a partial DNA intercalator. In silico screening indicated that the [AuIII (CNC)Cl]+ complex can target DNA three-way junctions with good specificity, several other regular B-DNA forms, and Z-DNA. Multiple hydrophobic π-type interactions involving T and A bases appear to be important for B-form DNA binding, while phosphate O⋅⋅⋅Au interactions evidently underpin Z-DNA binding. The CNC ligand effectively stabilizes the AuIII ion, preventing reduction in the presence of glutathione. Both the redox stability and DNA affinity of the hit compound might be key factors underpinning its cytotoxicity in vitro.

Synthesis of 6-Membered-Ring Fused Thiazine-Dicarboxylates and Thiazole-Pyrimidines via One-Pot Three-Component Reactions.

A facile and efficient one-pot three-component reaction method for the synthesis of thiazine-dicarboxylates is reported. Reaction of an isocyanide and dialkyl acetylenedicarboxylate with 2-amino-4H-1,3-thiazin-4-one derivatives containing both an acidic proton and an internal nucleophile gave the products in good yields of 76-85%. The reactivity of dialkyl acetylenedicarboxylates was further tested in the synthesis of thiazole-pyrimidines where a two-component reaction of 2-aminothiazole with dialkyl acetylenedicarboxylates was successfully converted to a more efficient three-component reaction of a thiourea, α-haloketone and dialkyl acetylenedicarboxylate (DMAD/DEtAD) to give thiazole-pyrimidines in good yields of 70-91%.

Total synthesis of ent-pavettamine.

Pavettamine, a plant toxin first isolated from Pavetta harborii in 1995, was previously identified as a polyamine with C 2 symmetry and a 1,3-syn-diol moiety on a C10 carbon backbone - one of very few substituted polyamines to be isolated from nature. Its absolute configuration was later established by our first reported total synthesis in 2010. Herein we report the first total synthesis of the enantiomer of pavettamine, ent-pavettamine. The symmetrical structure of the molecule allows for the synthesis of a common C5 fragment that can be divergently transformed into two synthons for later convergent coupling to furnish the target carbon framework. Based on the success of the protocol we employed for the synthesis of the naturally occurring pavettamine, (S)-malic acid was again the starting material of choice for the synthesis of the two individual C5 fragments, with strategic differences in terminal-group manipulation allowing for the synthesis of ent-pavettamine rather than pavettamine. Chain extension and stereoselective ketone reduction were achieved using the (R)-methyl p-tolyl sulfoxide chiral auxiliary to give the desired 1,3-syn-diol C5 unit. A protecting-group strategy was also developed for the orthogonal protection of the alcohol and amine functional groups as they were unveiled. The functionalized C5 fragments were coupled via reductive amination revealing the C10 carbon backbone. Deprotection of the alcohol and amine functional groups successfully provided ent-pavettamine as a TFA salt.

Synthesis and Photophysical Properties of T-Shaped Coinage-Metal Complexes.

The photophysical properties of a series of T-shaped coinage d10 metal complexes, supported by a bis(mesoionic carbene)carbazolide (CNC) pincer ligand, are explored. The series includes a rare new example of a tridentate T-shaped AgI complex. Post-complexation modification of the AuI complex provides access to a linear cationic AuI complex following ligand alkylation, or the first example of a cationic square planar AuIII -F complex from electrophilic attack on the metal centre. Emissions ranging from blue (CuI ) to orange (AgI ) are obtained, with variable contributions of thermally-dependent fluorescence and phosphorescence to the observed photoluminescence. Green emissions are observed for all three gold complexes (neutral T-shaped AuI , cationic linear AuI and square planar cationic AuIII ). The higher quantum yield and longer decay lifetime of the linear gold(I) complex are indicative of increased phosphorescence contribution.

Fischer Carbene Complexes of Iridium(I) for Application in Catalytic Transfer Hydrogenation.

New examples of the very rare class of iridium(I) Fischer carbene complexes (FCCs) are reported from the facile transmetalation from group 6 FCCs. Postcomplexation modification of either the carbene ligand or the ancillary coligands results in a tunable IrI metal center, for unprecedented application as a (pre)catalyst in a benchmark transfer hydrogenation reaction. The introduction of an aminocarbene ligand with a pendant N-donor moiety capable of hemilabile coordination yielded the best catalytic results with turnover frequencies reaching 445 h-1 and requiring 0.1 mol % catalyst and 0.5 mol % base loading, respectively.

Glutamate 85 and glutamate 228 contribute to the pH-response of the soluble form of chloride intracellular channel 1.

The chloride intracellular channel protein, CLIC1, is synthesised as a soluble monomer that can reversibly bind membranes. Soluble CLIC1 is proposed to respond to the low pH found at a membrane surface by partially unfolding and restructuring into a membrane-competent conformation. This transition is proposed to be controlled by strategically located "pH-sensor" residues that become protonated at acidic pH. In this study, we investigate the role of two conserved glutamate residues, Glu85 in the N-domain and Glu228 in the C-domain, as pH-sensors. E85L and E228L CLIC1 variants were created to reduce pH sensitivity by permanently breaking the bonds these residues form. The structure and stability of each variant was compared to the wild type at both pH 7.0 and pH 5.5. Neither substitution significantly altered the structure but both decreased the conformational stability. Furthermore, E85L CLIC1 formed a urea-induced unfolding intermediate state at both pH 7 and pH 5.5 compared to wild-type and E228L CLIC1 which only formed the intermediate at pH 5.5. We conclude that Glu85 and Glu228 are two of the five pH-sensor residues of CLIC1 and contribute to the pH-response in different ways. Glu228 lowers the stability of the native state at pH 5.5, while Glu85 contributes both to the stability of the native state and to the formation of the intermediate state. By putting these interactions into the context of the three previously described CLIC1 pH-sensor residues, we propose a mechanism for the conversion of CLIC1 from the soluble state to the pre-membrane form.

The synthesis of a corrole analogue of aquacobalamin (vitamin B12a) and its ligand substitution reactions.

The synthesis of a Co(III) corrole, [10-(2-[[4-(1H-imidazol-1-ylmethyl)benzoyl]amino]phenyl)-5,15-diphenylcorrolato]cobalt(III), DPTC-Co, bearing a tail motif terminating in an imidazole ligand that coordinates Co(III), is described. The corrole therefore places Co(III) in a similar environment to that in aquacobalamin (vitamin B12a, H2OCbl(+)) but with a different equatorial ligand. In coordinating solvents, DPTC-Co is a mixture of five- and six-coordinate species, with a solvent molecule occupying the axial coordination site trans to the proximal imidazole ligand. In an 80:20 MeOH/H2O solution, allowed to age for about 1 h, the predominant species is the six-coordinate aqua species [H2O-DPTC-Co]. It is monomeric at least up to concentrations of 60 µM. The coordinated H2O has a pKa = 9.76(6). Under the same conditions H2OCbl(+) has a pKa = 7.40(2). Equilibrium constants for the substitution of coordinated H2O by exogenous ligands are reported as log K values for neutral N-, P-, and S-donor ligands, and CN(-), NO2(-), N3(-), SCN(-), I(-), and Cys in 80:20 MeOH/H2O solution at low ionic strength. The log K values for [H2O-DPTC-Co] correlate reasonably well with those for H2OCbl(+); therefore, Co(III) displays a similar behavior toward these ligands irrespective of whether the equatorial ligand is a corrole or a corrin. Pyridine is an exception; it is poorly coordinated by H2OCbl(+) because of the sterically hindered coordination site of the corrin. With few exceptions, [H2O-DPTC-Co] has a higher affinity for neutral ligands than H2OCbl(+), but the converse is true for anionic ligands. Density functional theory (DFT) models (BP86/TZVP) show that the Co-ligand bonds tend to be longer in corrin than in corrole complexes, explaining the higher affinity of the latter for neutral ligands. It is argued that the residual charge at the metal center (+2 in corrin, 0 in corrole) increases the affinity of H2OCbl(+) for anionic ligands through an electrostatic attraction. The topological properties of the electron density in the DFT-modeled compounds are used to explore the nature of the bonding between the metal and the ligands.

Di-chlorido-dimethyl-bis-(thio-urea-κS)tin(IV).

The title compound, [Sn(CH3)2Cl2(CH4N2S)2], crystallizes with two half-mol-ecules in the asymmetric unit. Both mol-ecules are completed by inversion symmetry with the two Sn(IV) atoms located on inversion centers. The metal atoms have distorted octa-hedral coordination environments defined by two Cl atoms, two C atoms of methyl groups and two thio-urea S atoms. In the crystal, mol-ecules are linked via N-H⋯Cl and N-H⋯S hydrogen bonds, forming a three-dimensional structure.

Repeat cytoreduction with Hyperthermic Intraperitoneal chemotherapy in patients with peritoneal disease: A 5-year retrospective analysis.

BACKGROUND: Cytoreductive surgery with Hyperthermic Intraperitoneal Chemotherapy (CR-HIPEC) is a locorregional surgical therapy applied in patients with peritoneal-only metastatic disease of primary abdominal malignancies. Integrated in a multimodal treatment, CR-HIPEC is associated with increased overall survival. In cases of peritoneal-site only relapse, it may be carried out more than once. METHODS: Patients who received a CR-HIPEC between January 2016 and December 2020 at Instituto Português de Oncologia do Porto, Portugal were included in a unicentric, retrospective, observational study. Short- and long-term outcomes after surgery were analyzed. RESULTS: In this period, 259 CR-HIPEC were performed on 248 patients. Of these, 31 were CR-HIPEC repeats, with 6 being the third HIPEC in the same patient. Of the 31 cases, 15 (48.4 %) had an appendicular origin. Mean PCI in re-HIPEC group was 10.6 (SD ± 7.1). No significant differences in baseline characteristics between the first and re-HIPEC groups were found, except for mean PCI, higher in the 1st HIPEC group (p = 0.047). In re-HIPEC group, major complications rate (CT-CAE 3-4) was 12.9 % (n = 4), without postoperative mortality. The 1st and re-HIPEC group had similar morbidity rates and hospitalization time. With a median follow-up time of 44 months, relapse rate after repeat CR-HIPEC was 45.2 % (n = 14), with a mean overall survival (OS) of 68.7 months and 5-year OS of 78 %. CONCLUSIONS: Repeat CR-HIPEC is a safe approach with an acceptable complication rate for its complexity, associated with a survival benefit in selected patients. It should be presented as a valid therapeutic option in recurrent peritoneal disease.

Trueness of Extraoral Digital Impressions for Full-Arch Implant Impressions-In Vitro Study.

Direct scanning of silicone impressions is a valid technique. However, studies in implant-supported rehabilitations are lacking. This in vitro study aims to compare the trueness of impressions obtained with two types of silicone and their corresponding stone casts, using two laboratory scanners in a full-arch implant rehabilitation. A master cast with six dental implants was scanned with a 12-megapixel scanner to obtain a digital master cast. Ten implant impressions were made using two silicones (Zhermack and Coltene) with the open-tray technique. The impressions and stone casts were scanned by two extraoral scanners (Identica T500, Medit; and S600 ARTI, Zirkonzhan). Trueness was assessed by comparing linear and angular distances in digital casts with the master cast. A p < 0.05 significance level was considered. The results showed that for the linear measurements, 72% were higher than the master cast measurements, and no consistent pattern was observed in the angular measurements. The greatest deviations were detected between the most posterior implants, with mean values ranging between 173 and 314 µm. No significant differences were found between scanners. However, differences were observed in the distances between silicones (46.7%) and between impressions and stone casts (73.3%). This work demonstrates that the direct scanning of silicone impressions yields results comparable to those obtained from scanning gypsum casts in full-arch implant-supported rehabilitation.

Accuracy of Silicone Impressions and Stone Models Using Two Laboratory Scanners: A 3D Evaluation.

PURPOSE: To evaluate the in vitro accuracy of impressions obtained with two silicone and corresponding stone models using two laboratory scanners. MATERIALS AND METHODS: A master model with synthetic resin teeth with two single-unit crown preparations was created and scanned using a 12-megapixel scanner. Five conventional impressions of the physical model were prepared with different silicone impression systems (Zhermack and Coltene) using the double-mix technique and poured with gypsum. The impressions and stone models obtained were scanned using two extraoral scanning systems (Identica T500, Medit; S600 ARTI, Zirkonzahn). All best-fit superimpositions of the teeth areas were conducted between the master model and the scans of the impressions and models obtained with the two scanners. A P < .05 level was considered significant. RESULTS: The Identica T500 Medit scanner showed an accuracy of 102.34 (89.67, 115.01) µm for Coltene silicone and 79.51 (67.82, 91.21) µm for Zhermack silicone, while the S600 ARTI Zirkonzhan scanner presented 110.79 (98.24, 123.33) µm and 91.91 (81.29, 102.54) µm, respectively, with significant differences between scanners for Zhermack silicone (P = .008) and for the corresponding stone models (P = .002). Zhermack silicone presented overall discrepancies lower than Coltene silicone, with statistically significant differences in both scanners analyzed (P < .001; P = .017). However, the discrepancies found were within clinically acceptable values. With the Zirkonzahn scanner, discrepancies found in the Zhermack impressions were lower than in the corresponding stone models (P < .001). CONCLUSIONS: The direct digitization of silicone impressions with laboratory scanners presented comparable results to conventional techniques with stone models.

Tungsten-183 NMR study of cis-[W(CO)4(PPh3)(4-RC5H4N)]; effect of varying the σ donor strength of the pyridine.

Tungsten-183 NMR data are reported for the complexes cis-[W(CO)4(PPh3)(4-RC5H4N)] (R = H, Me, Ph, COMe, COPh, OMe, NMe2, Cl, NO2). The (183)W chemical shift (obtained by indirect detection using (31)P) is found to correlate with the Hammett σ function for the group R, with (183)W shielding increasing approximately linearly with the donor strength of the pyridine over a range of 93 ppm. The X-ray structures of cis-[W(CO)4(PPh3)(4-MeOC5H4N)] and cis-[W(CO)4(PPh3)(4-PhCOC5H4N)] are also reported.

3-Methyl-1-tosyl-1H-indole-2-carbaldehyde.

The title indole derivative, C(17)H(15)NO(3)S, crystallizes with two independent mol-ecules in the asymmetric unit. The benzene ring of the tosyl group is almost perpedicular to the indole ring in both mol-ecules, with inter-planar angles of 82.60 (5)° and 81.82 (6)°. The two mol-ecules are, as a consequence, able to form an almost centrosymmetric non-bonded dimer, in which the molecules are linked by pairs of C-H⋯π inter-actions. The crystal structure displays a three-dimensional network of C-H⋯O inter-actions. A π-π inter-action occurs between inversion-related indole rings with a centroid-centroid distance of 3.6774 (16) Šand an inter-planar angle of 1.53 (15)°. This inter-action leads to a stacking of mol-ecules along the a axis.

Hyperthermic Intraperitoneal Chemotherapy in Gastric Cancer: A Clinical Case Involving Long-Term Survival.

Peritoneal metastasis is the most common pattern of synchronous and metachronous dissemination in gastric cancer (GC) and is associated with a poor prognosis. Even though systemic chemotherapy is the standard of care, the optimal therapeutic approach to peritoneal disease in this setting is yet to be defined. We present a case of a 26-year-old female diagnosed with locally advanced GC who developed peritoneal carcinomatosis (PC). The patient underwent cytoreductive surgery (CRS) along with hyperthermic intraperitoneal chemotherapy (HIPEC) with complete remission. She remained disease-free after six years, presenting with peritoneal recurrence 70 months after the procedure. This report describes a rare case of long-term survival following a controversial therapeutic approach.

Limited Antineutrophil Cytoplasmic Antibodies (ANCA)-Negative Granulomatosis With Polyangiitis: Successful Response to Rituximab.

Granulomatosis with polyangiitis (GPA), a systemic vasculitis, is commonly characterized by the presence of antineutrophil cytoplasmic antibodies (ANCA). However, a subset of patients with limited disease may exhibit ANCA negativity. In this article, we report the case of a 40-year-old female diagnosed with GPA with intolerance to methotrexate titration and glucocorticoid therapy, leading to the initiation of rituximab treatment. Subsequently, the patient exhibited sustained clinical, laboratory, and radiological improvement. The identification of limited GPA has important therapeutic implications as the effectiveness of the medical treatment in ANCA-negative GPA may differ. Rituximab has emerged as an optimal treatment, irrespective of ANCA status, offering prolonged responses and a favorable tolerance profile in these patients.

Do Pentavalent (DTwP-Hib-HBV) vaccines have sex-differential nonspecific effects? An observational study.

Vaccines may alter the ability to combat infections unrelated to the target disease, i.e. have "nonspecific effects." The non-live Diphtheria-Tetanus-Pertussis vaccine (DTP) has been associated with increased child mortality, especially for females. In 2008, the DTP-containing Pentavalent vaccine replaced DTP vaccine in Guinea-Bissau. We investigate female relative to male mortality after Penta vaccination. In Guinea-Bissau, Bandim Health Project (BHP) registered children's vaccination and vital status at biannual village visits and provided vaccines. Among children Penta-vaccinated by BHP, we compared mortality of males and females in Cox proportional hazards models. Children aged 6 weeks to 8 months entered the analysis at the date of vaccination and were followed for up to 6 months. Between September 2008 and December 2017, 33,989 children aged 6 weeks to 8 months were under surveillance. Of these 12,753 (females: 6,363; males: 6,390) received Penta by the BHP and entered the study contributing with 19,667 observations. The mortality rate following Penta vaccination was 25.2 per 1,000 person years for females and 26.6 for males, resulting in an adjusted Female/Male mortality rate ratio of (F/M aMRR) 1.01 (0.82-1.25). The association between sex and mortality differed by timeliness of vaccination, F/M aMRR: 0.62 (0.41-0.93) for children vaccinated below median age, and F/M aMRR: 1.38 (0.90-2.13) for children vaccinated above median age. We did not find higher overall mortality in females than males after Penta vaccination. Our findings suggest that mortality differences between males and females following Penta vaccination may depend on timeliness of Penta vaccination.

Role of individual histidines in the pH-dependent global stability of human chloride intracellular channel 1.

Chloride intracellular channel proteins exist in both a soluble cytosolic form and a membrane-bound form. The mechanism of conversion between the two forms is not properly understood, although one of the contributing factors is believed to be the variation in pH between the cytosol (~7.4) and the membrane (~5.5). We systematically mutated each of the three histidine residues in CLIC1 to an alanine at position 74 and a phenylalanine at positions 185 and 207. We examined the effect of the histidine-mediated pH dependence on the structure and global stability of CLIC1. None of the mutations were found to alter the global structure of the protein. However, the stability of H74A-CLIC1 and H185F-CLIC1, as calculated from the equilibrium unfolding data, is no longer dependent on pH because similar trends are observed at pH 7.0 and 5.5. The crystal structures show that the mutations result in changes in the local hydrogen bond coordination. Because the mutant total free energy change upon unfolding is not different from that of the wild type at pH 7.0, despite the presence of intermediates that are not seen in the wild type, we propose that it may be the stability of the intermediate state rather than the native state that is dependent on pH. On the basis of the lower stability of the intermediate in the H74A and H185F mutants compared to that of the wild type, we conclude that both His74 and His185 are involved in triggering the pH changes to the conformational stability of wild-type CLIC1 via their protonation, which stabilizes the intermediate state.