Binding of [3H]-2-isobutyl-3-methoxypyrazine to cow olfactory mucosa

The odorant 2-isobutyl-3-methoxypyrazine binds to cow olfactorymucosa homogenate. The complex, which can be separated by gelfiltration on Sephadex G-100, appears to be made up of fourmacromolecular species. No significant binding has been measuredwith respiratory epithelium. The binding disappears after treatmentwith proteolytic enzymes, or in a SDS containing buffer, thusindicating that the receptors are proteins. Complete loss ofbinding capacity has been also observed as a consequence ofdialysis: this suggests the involvement of a low molecular weightcomponent.     

Influence of the annual flood-pulse on catch per unit effort,condition and reproduction of Clarias gariepinus from the upper Okavango Delta,Botswana

Catch per unit effort (CPUE), length, weight and maturity data for Clarias gariepinus were collected during monthly gillnet surveys in the upper Okavango Delta between 2001 and 2009 to investigate their relationship with the annual flood-pulse. CPUE, condition factor (K) and the proportion of ripe-running fish (P_RR) in the population followed a unimodal annual cycle that could be modelled using water temperature and flood-pulse hydrology. Increased CPUE during declining water levels was most likely a result of feeding migrations and aggregation behaviour. The observed increase in K during low floods in October and November preceded the increase in P_RR, which increased mainly with increasing temperature but appeared less dependent on flow. This study provided quantitative evidence that the biology of fish in the Okavango Delta is mainly dependent on the annual flood regime and, therefore, that conservation efforts should be focused on maintaining natural flow patterns in the face of climate change and potential water extraction schemes upstream.     

Effect of Nodularia harveyana biomass on the incidence of root-knot nematode (Meloidogyne incognita) in tomato

An acetone extract of Nodularia harveyana wasshown to be toxic to the free-living nematode Cephaloboides oxycerca. This antagonistic effect wastested in pot culture trials with lyophilized biomasson gall induction by the root-knot nematode Meloidogyne incognita, using different methods ofapplication of the cyanobacterial biomass to thetomato plants. The trials revealed a possibleutilization of biomass of this cyanobacterium as aprotection agent against this phytoparasite.     

Extensive activation,tissue trafficking,turnover and functional impairment of NK cells in COVID-19 patients at disease onset associates with subsequent disease severity

The SARS-CoV-2 infection causes severe respiratory involvement (COVID-19) in 5–20% of patients through initial immune derangement, followed by intense cytokine production and vascular leakage. Evidence of immune involvement point to the participation of T, B, and NK cells in the lack of control of virus replication leading to COVID-19. NK cells contribute to early phases of virus control and to the regulation of adaptive responses. The precise mechanism of NK cell dysregulation is poorly understood, with little information on tissue margination or turnover. We investigated these aspects by multiparameter flow cytometry in a cohort of 28 patients hospitalized with early COVID-19.Relevant decreases in CD56^brightCD16+/- NK subsets were detected, with a shift of circulating NK cells toward more mature CD56^dimCD16+KIR+NKG2A+ and “memory” KIR+CD57+CD85j+ cells with increased inhibitory NKG2A and KIR molecules. Impaired cytotoxicity and IFN-γ production were associated with conserved expression of natural cytotoxicity receptors and perforin. Moreover, intense NK cell activation with increased HLA-DR and CD69 expression was associated with the circulation of CD69+CD103+ CXCR6+ tissue-resident NK cells and of CD34+DNAM-1^brightCXCR4+ inflammatory precursors to mature functional NK cells. Severe disease trajectories were directly associated with the proportion of CD34+DNAM-1^brightCXCR4+ precursors and inversely associated with the proportion of NKG2D+ and of CD103+ NK cells.Intense NK cell activation and trafficking to and from tissues occurs early in COVID-19, and is associated with subsequent disease progression, providing an insight into the mechanism of clinical deterioration. Strategies to positively manipulate tissue-resident NK cell responses may provide advantages to future therapeutic and vaccine approaches.     

Histidine decarboxylase, DOPA decarboxylase, and vesicular monoamine transporter 2 expression in neuroendocrine tumors: immunohistochemical study and gene expression analysis.

Histidine decarboxylase (HDC) and vesicular monoamine transporter 2 (v-MAT2) are involved in the biosynthesis and storage of histamine. DOPA decarboxylase (DDC) is involved in the biosynthesis of a variety of amines and shares a high degree of homology with HDC. HDC and v-MAT2 immunoreactivities (IR) have recently been detected in well-differentiated neuroendocrine tumors (WDNETs) and poorly differentiated neuroendocrine carcinomas (PDNECs) of various sites and have been proposed as general endocrine markers. We evaluated HDC and v-MAT2 IR in a series of 117 WDNETs and PDNECs from different sites. Western blotting analysis was performed to verify the specificity of anti-DDC and anti-HDC antibodies. Real-time RT-PCR was performed using specific probes for HDC and DDC on 42 cases, examined also for DDC IR. HDC and v-MAT2 IR were observed in the majority of WDNETs and PDNECs of all sites and HDC-IR cases were always also DDC-IR. In contrast, high levels of HDC mRNA were detected only in the gastroenteropancreatic WDNETs, which did not show increased DDC mRNA levels. On the other hand, bronchial carcinoids and lung PDNECs showed high DDC mRNA levels, but nearly undetectable HDC mRNA levels. Western blotting analysis showed a cross-reaction between anti-HDC and anti-DDC antibodies. HDC should not be considered as a general endocrine marker and HDC IR in bronchial carcinoids and PDNECs of the lung can probably be attributed to a cross-reaction with DDC.     

SAM68 is a physiological regulator of SMN2 splicing in spinal muscular atrophy

Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by loss of motor neurons in patients with null mutations in the SMN1 gene. The almost identical SMN2 gene is unable to compensate for this deficiency because of the skipping of exon 7 during pre–messenger RNA (mRNA) processing. Although several splicing factors can modulate SMN2 splicing in vitro, the physiological regulators of this disease-causing event are unknown. We found that knockout of the splicing factor SAM68 partially rescued body weight and viability of SMAΔ7 mice. Ablation of SAM68 function promoted SMN2 splicing and expression in SMAΔ7 mice, correlating with amelioration of SMA-related defects in motor neurons and skeletal muscles. Mechanistically, SAM68 binds to SMN2 pre-mRNA, favoring recruitment of the splicing repressor hnRNP A1 and interfering with that of U2AF65 at the 3′ splice site of exon 7. These findings identify SAM68 as the first physiological regulator of SMN2 splicing in an SMA mouse model.     

Response of calcareous nannofossil assemblages to paleoenvironmental changes through the mid-Pleistocene revolution at Site 1090 (Southern Ocean)

Quantitative study on calcareous nannofossil assemblages has been performed in high time resolution (2–3 kyr) at the Ocean Drilling Program Site 1090. The location of this site in the Southern Ocean is crucial for the comprehension of thermohaline circulation and frontal boundary dynamics, and for testing the employ of nannoflora as paleoceanographical tool. The chronologically well constrained investigated record spans between Marine Isotope Stage (MIS) 35 and 15, through an interval of global paleoclimate and paleoceanographical modification also known as mid-Pleistocene revolution (MPR). Measures of ecological (Shannon–Weaver diversity and paleoproductivity) and dissolution indices together with spectral and wavelet analyses carried out on the acquired time series provide valuable information for interpretation of data in terms of paleoecology and paleoceanography. Assemblages are mainly represented by dominant small Gephyrocapsa, common Calcidiscus leptoporus s.l., Coccolithus pelagicus s.l., Gephyrocapsa (4-5.5 μm), the extinct Pseudoemiliania lacunosa and Reticulofenestra spp. (R. asanoi and Reticulofenestra sp.). Morphotypes discriminated within Calcidiscus leptoporus s.l. and Coccolithus pelagicus s.l., reveal that they may have had different ecological preferences during Pleistocene with respect to the present. The composition and fluctuation in nannofossil assemblage and their comparison with the available Sea Surface Temperature (SST) and C-org curves suggest a primary ecological response to paleoenvironmental changes; relationships to different surface water features and boundary dynamics, as well as to different efficiencies and motions of the intermediate and deep water masses have been inferred. A more northward position of Subantarctic Front (SAF) during most of the Early Pleistocene record has been highlighted based on assemblage composition characterised by common Calcidiscus leptoporus s.l., Coccolithus pelagicus s.l., medium Gephyrocapsa (4–5.5 μm), and by the rarity or absence of Umbilicosphaera spp., Rhabdosphaera spp., Pontosphaera spp., Oolithotus fragilis. Exceptions are the more intense interglacials MIS 31, 17, and probably MIS 15, when a southward displacement of frontal system occurred, coincident with peaks in abundance of Helicosphaera spp. and Syracosphaera spp. Higher nutrient content and more dynamic conditions occurred between MIS 32 and MIS 25, in relation to shallower location of nutrient-rich Antarctic Intermediate Water (AAIW) core and to reduction of glacial–interglacial variability. A nannofossil barren interval is coincident with the known stagnation of South Atlantic deep water circulation during MIS 24, when North Atlantic Deep Water (NADW) was reduced or suppressed and an enhanced northward deep penetration of the more corrosive Circumpolar Deep Water (CPDW) took place. An event of strong instability in nutricline dynamics characterised the transition MIS 23–22 as suggested by sharp fluctuations in paleoproductivity proxies, linked to major changes in oceanographic circulation and to the first distinct increase of larger ice volumes at this time. From MIS 21 upward the nannofossil variations seem to be primarily controlled by glacial–interglacial cyclicity and temperature fluctuations. The cyclic fluctuation recognised in nannofossil abundance seems to be linked to orbitally-forced climatic variation, primarily to the obliquity periodicity recorded in the patterns of C. leptoporus intermediate (5–8 μm) and C. pelagicus pelagicus (6–10 μm); however no obvious and linear relations may be always observed between nannoflora fluctuation and Milankovitch parameters, suggesting more complex and unclear relationships between nannofossils and environmental change.     

The Middle Miocene climatic transition in the Southern Ocean: Evidence of paleoclimatic and hydrographic changes at Kerguelen plateau from planktonic foraminifers and stable isotopes

Middle Miocene (14.8–11.9 Ma) deep-sea sediments from ODP Hole 747A (Kerguelen Plateau, southern Indian Ocean) contain abundant, well-preserved and diverse planktonic foraminiferal assemblages. A detailed study of the climatic and hydrographic changes that occurred in this region during the Middle Miocene Climatic Transition led to the identification of an intense cooling phase (the Middle Miocene Shift). Abundance fluctuations of planktonic foraminiferal species with different paleoclimatic affinities, and oxygen and carbon stable isotopes have been integrated in a multi-proxy approach. Reconstruction of changes in foraminiferal faunal composition and diversity through time were the basis for identification of three foraminiferal biofacies. The most prominent faunal change took place at 13.8 Ma, when a fauna with warm-water affinity (marked by high abundance of Globorotalia miozea group and Globoturborotalita woodi plexus) was replaced by an oligotypic, opportunistic fauna with typical polar characters and dominated by neogloboquadrinids. This faunal change is interpreted as the result of foraminiferal migration from adjacent bioprovinces, caused by modifications in climate and hydrography. A positive 2.0‰ shift in δ¹⁸O (interpreted as the Mi3 event) and a related positive 1.0‰ shift in δ¹³C (corresponding to the CM6 event) accompanied this faunal turnover. These are interpreted to reflect substantial reorganization of Southern Ocean waters, the northward migration of the Polar Front and a strong increase in primary productivity. The second faunal change took place at 12.9 Ma and was characterized by the gradual decrease in abundance of the neogloboquadrinids and the recovery of Globorotalia praescitula/scitula group and Globigerinita glutinata. A positive 1.5‰ shift in δ¹⁸O (interpreted as the Mi4 event) and a concurrent gradual negative shift in δ¹³C accompanied this faunal change, witnessing further modifications of the climate/ocean system. Variations in sea surface temperature, considered as the main factor causing changes of surface hydrography at the Kerguelen Plateau, seem to have been driven by obliquity and long-term eccentricity, thus suggesting a key role played by the astronomical forcing on the evolution of Southern Ocean dynamics during the Middle Miocene. Also an evident 1.2 Myr modulation of the δ¹³C record suggests a main control of the long-term obliquity cycles on the carbon cycle dynamics. Particularly, the Mi3/CM6 events exactly fit with a node of the 1.2 Myr modulation cycles. This confirms the key role played by orbital parameters on high-latitude temperatures and Antarctic ice volume, and indirectly on global carbon burial and/or productivity. This climatic transition was marked also by changes in surface hydrography. From 14.8 to 13.8 Ma an intermediate-strength thermocline controlled by seasonality developed just below the photic zone. Weaker seasonality characterized the interval from 13.8 to 12.9 Ma, when the thermocline became shallower and sharper and favored intermediate-water foraminifers. From 12.9 Ma, seasonality increased again and an intermediate-strength thermocline re-developed.